研究生: |
彭詩涵 Peng, Shih-Han |
---|---|
論文名稱: |
Lunasin對肥胖因子影響MCF-7與MDA-MB-231人類乳癌細胞生長之探討 The effects of lunasin on the growth of obesity-mediated MCF-7 and MDA-MB-231 human breast cancer cells |
指導教授: |
謝佳倩
Hsieh, Chia-Chien |
學位類別: |
碩士 Master |
系所名稱: |
人類發展與家庭學系 Department of Human Development and Family Studies |
論文出版年: | 2018 |
畢業學年度: | 106 |
語文別: | 中文 |
論文頁數: | 109 |
中文關鍵詞: | Lunasin 、肥胖 、乳癌 、巨噬細胞 |
英文關鍵詞: | Lunasin, Obesity, Breast Cancer, Macrophage |
DOI URL: | http://doi.org/10.6345/THE.NTNU.DHDFS.033.2018.A06 |
論文種類: | 學術論文 |
相關次數: | 點閱:166 下載:5 |
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流行病學研究顯示,過重或肥胖會增加女性罹患乳癌的風險,而肥胖過程中脂肪組織會有巨噬細胞浸潤情形,伴隨著促發炎性細胞激素的分泌而營造出一個慢性發炎的環境,適合腫瘤發展。此外,過多脂肪累積會增加aromatase的表現與活性,導致雌二醇生成增加,促使乳癌惡化。Lunasin為一種子胜肽,由43個胺基酸組成,目前研究證實具有抗腫瘤、抗發炎、抗氧化…等生理功能。然而Lunasin對肥胖相關人類乳癌細胞中的發炎介質、雌激素及芳香酶表現仍然未知。本實驗目的為探討Lunasin的介入是否會抑制肥胖微環境下雌激素依賴型MCF-7細胞及非依賴型MDA-MB-231乳癌細胞的生長並抑制其發炎反應及芳香酶表現。第一部分探討肥胖微環境是否影響乳癌發展。結果顯示在肥胖微環境下,以DMBA誘發癌化之NIH/3T3其foci數量會增加。在動物實驗發現,以DMBA誘發肥胖小鼠的乳癌腫瘤中,其腫瘤中細胞增殖能力(Ki67)與巨噬細胞浸潤(F4/80)的表現增加,副睪脂肪的M1型巨噬細胞(CD11c)及F4/80的表現也會上升,高脂飲食會降低M2型巨噬細胞(CD206)的表現,而Lunasin介入可抑制高脂飲食中的F4/80及CD11c的表現。第二部分為探討Lunasin對兩株雌激素依賴型相異的人類乳癌細胞之影響。結果顯示,MCF-7細胞在48小時之IC50為92.5 μM而MDA-MB-231細胞為136.3 μM。將細胞培養在3T3脂肪細胞條件培養液(Adipocyte conditioned medium, Ad-CM)環境下,Lunasin的處理皆能顯著抑制其兩株細胞的存活率。在細胞週期的部分,肥胖微環境下,Lunasin有將MCF-7細胞停滯在G2/M期的能力。細胞活性分析中,無論在有無Ad-CM的環境下, Lunasin的介入皆會抑制MCF-7的細胞活性,而MDA-MB-231僅在新鮮培養基下降低。另外,兩株細胞在新鮮培養基下經Lunasin處理後細胞凋亡皆增加,且芳香酶活性皆下降。
綜上所述,Lunasin可降低肥胖小鼠巨噬細胞的發炎反應,抑制乳癌細胞生長,並可降低乳癌細胞活性,增加細胞凋亡,並抑制芳香酶活性。因此,推測出富含Lunasin的飲食型態可能有助於乳癌患者的輔助治療,尤其是雌激素依賴型的乳癌。
The epidemiological studies have showed that the women with overweight or obesity have higher risk developed breast cancer. In adipogenesis, macrophages infiltrate into adipose tissue and accompany pro-inflammatory mediator secretions promoting cancer progression. In addition, excecive fat accumulation increase the expression and activity of aromatase, causing estradiol overproduction and promote the progression of breast cancer. Lunasin is a soy pepride which consist of 43 amino acids, the bioactivities of lunasin on chemopreventation, anti-inflammation and anti-oxidation have been widely studied. However, the effect of lunasin on obesity-related inflammation mediators secretion, estrogen production and aromatase expression in breast cancer cells are still uncertained. The aim of this work is to investigate whether lunasin can inhibit the growth of MCF-7 and MDA-MB-231 cells, and downregulate the inflammation in the microenvironment. First part is to find out the effect of obesity-related microenvironment on the progression of breast cancer. The results showed that that the number of DMBA-induced foci formation upregulated in obesity microenvironment in vitro studied. In vivo, F4/80, a macrophages infiltration marker, and cell proliferation increased in DMBA-induced mammary tumor in obese mice. Also, F4/80 and CD11c, a M1 macrophages marker, increased in Epididymal adipose tissue when DMBA intervention. Additionally, CD206, a M2 macrophages marker, decreased in obese mice. In addition, lunasin inhibit F4/80 and CD11c in obese mice. Second part is to investigate the effect of lunasin on estrogen dependent and estrogen independent breast cancer cells. The result revealed that after treatment with lunasin for 48h, the IC50 values in MCF-7 cells is 92.50 μM and in MDA-MB-231 cell is 136.3 μM. When incubate in 3T3-L1 adipocyte conditioned medium(Ad-CM), lunasin can inhibit cell viability in both MCF-7 and MDA-MB-231, and cell cycle arrested at G2/M phase in MCF-7. In cell vitality assay, no matter incubation with Ad-CM or not, lunasin intervention increase low vitality cells in MCF-7, but this result only found in MDA-MB-231 when incubation with fresh medium. At last, lunasin intervention increase apoptosis and decrease aromatase activity in both of breast cancer cells. In summary, lunasin downregulate inflammation in obese mice, inhibit the growth, vitality and aromatase activity and upregulate the apoptosis of breast cancer cells, which indicate that lunasin-enrich dietary life syle might be a promising adjuvant therapy to obesity-related cancer, especially estrogent dependent breast cancer.
王之璇(2017)。Aspirin抑制肥胖相關發炎因子促進乳癌細胞生長之探討。國立臺灣師範大學,台北市。
周美佳(2016)。探討種子胜肽Lunasin對於肥胖引起的發炎模式之免疫調節作用。國立臺灣師範大學,台北市。
黃渝珊(2015)。探討Lunasin及Aspirin的處理對脂肪細胞與乳癌細胞發炎與生長之影響。國立臺灣師範大學,台北市。
衛福部(17.03.2017).乳癌防治. Retrieved from ttps://www.hpa.gov.tw/Pages/Detail.aspx?nodeid=205&pid=1124 [Accessed 2017.09.24]
Abdalla, D. R., Aleixo, A. A. R., Murta, E. F., & Michelin, M. A. (2014). Innate immune response adaptation in mice subjected to administration of DMBA and physical activity. Oncology letters, 7(3), 886-890.
Ackerman, G. E., SMITH, M. E., MENDELSON, C. R., MACDONALD, P. C., & SIMPSON, E. R. (1981). Aromatization of androstenedione by human adipose tissue stromal cells in monolayer culture. The Journal of Clinical Endocrinology & Metabolism, 53(2), 412-417.
Ahima, R. S., & Osei, S. Y. (2008). Adipokines in obesity. In Obesity and Metabolism (Vol. 36, pp. 182-197). Karger Publishers.
Alshaker, H., Krell, J., Frampton, A. E., Waxman, J., Blyuss, O., Zaikin, A., Winkler, M., Stebbing, J., Yagüe,E. & Pchejetski, D. (2014). Leptin induces upregulation of sphingosine kinase 1 in oestrogen receptor-negative breast cancer via Src family kinase-mediated, janus kinase 2-independent pathway. Breast Cancer Research, 16(5), 426.
Altintas, M. M., Azad, A., Nayer, B., Contreras, G., Zaias, J., Faul, C., Reiser, J. & Nayer, A. (2011). Mast cells, macrophages, and crown-like structures distinguish subcutaneous from visceral fat in mice. Journal of lipid research, 52(3), 480-488.
Alvarez, A., Barisone, G. A., & Diaz, E. (2014). Focus formation: a cell-based assay to determine the oncogenic potential of a gene. Journal of visualized experiments: JoVE, (94).
Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, Hotta K, Shimomura I, Nakamura T, Miyaoka K, Kuriyama H, Nishida M, Yamashita S, Okubo K, Matsubara K, Muraguchi M, Ohmoto Y, Funahashi T, Matsuzawa Y. (1999) Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun. 2;257(1):79-83
Arita, Y., Kihara, S., Ouchi, N., Maeda, K., Kuriyama, H., Okamoto, Y., Kumada, M., Hotta, K., Nishida, Nishida, M., Takahashi, M., Nakamura, T., Shimomura, I., Muraguchi, M., Ohmoto, Y., Funahashi, T. & Nakamura, T. (2002). Adipocyte-derived plasma protein adiponectin acts as a platelet-derived growth factor-BB–binding protein and regulates growth factor–induced common postreceptor signal in vascular smooth muscle cell. Circulation, 105(24), 2893-2898.
Aupperlee, M. D., Zhao, Y., Tan, Y. S., Zhu, Y., Langohr, I. M., Kirk, E. L., Pirone, J.R., Troester, M.A., Schwartz, R.C. & Haslam, S. Z. (2015). Puberty-specific promotion of mammary tumorigenesis by a high animal fat diet. Breast Cancer Research, 17(1), 138.
Balaban, S., Shearer, R. F., Lee, L. S., van Geldermalsen, M., Schreuder, M., Shtein, H. C., Cairons, R., Thomas, K.C., Fazakerley, D.J., Grewal, T., Holst, J., Saunders, D.N. & Holst, J. (2017). Adipocyte lipolysis links obesity to breast cancer growth: adipocyte-derived fatty acids drive breast cancer cell proliferation and migration. Cancer & metabolism, 5(1), 1.
Barbieri, I., Pensa, S., Pannellini, T., Quaglino, E., Maritano, D., Demaria, M., Voster, A., Turkson, J., Cavallo, F., Watson, C.J., Provero, P., Musiani, P. & Provero, P. (2010). Constitutively active Stat3 enhances neu-mediated migration and metastasis in mammary tumors via upregulation of Cten. Cancer research, 70(6), 2558-2567.
Batra, P., & Sharma, A. K. (2013). Anti-cancer potential of flavonoids: recent trends and future perspectives. 3 Biotech, 3(6), 439-459.
Baum, M., Budzar, A. U., Cuzick, J., Forbes, J., Houghton, J. H., Klijn, J. G., & Sahmoud, T. (2002). Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial. Lancet (London, England), 359(9324), 2131-2139.
Benizri, E., Ginouves, A., & Berra, E. (2008). The magic of the hypoxia-signaling cascade. Cellular and molecular life sciences, 65(7-8), 1133-1149.
Bettelli, E., Carrier, Y., Gao, W., Korn, T., Strom, T. B., Oukka, M., Weiner, H.L. & Kuchroo, V. K. (2006). Reciprocal developmental pathways for the generation of pathogenic effector T H 17 and regulatory T cells. Nature, 441(7090), 235.
Bianchini, F., Kaaks, R., & Vainio, H. (2002). Overweight, obesity, and cancer risk. The lancet oncology, 3(9), 565-574.
Bocca, C., Ievolella, M., Autelli, R., Motta, M., Mosso, L., Torchio, B., Bozzo, F., Cannito, S., Paternostro, C., Colombatto, S., Parola, M. & Parola, M. (2014). Expression of Cox-2 in human breast cancer cells as a critical determinant of epithelial-to-mesenchymal transition and invasiveness. Expert opinion on therapeutic targets, 18(2), 121-135.
Boutens, L., & Stienstra, R. (2016). Adipose tissue macrophages: going off track during obesity. Diabetologia, 59(5), 879-894.
Brueggemeier, R. W., Díaz-Cruz, E. S., Li, P. K., Sugimoto, Y., Lin, Y. C., & Shapiro, C. L. (2005). Translational studies on aromatase, cyclooxygenases, and enzyme inhibitors in breast cancer. The Journal of steroid biochemistry and molecular biology, 95(1-5), 129-136.
Bulun, S. E., Chen, D., Moy, I., Brooks, D. C., & Zhao, H. (2012). Aromatase, breast cancer and obesity: a complex interaction. Trends in Endocrinology & Metabolism, 23(2), 83-89.
Cam, A., & de Mejia, E. G. (2012). RGD‐peptide Lunasin inhibits Akt‐mediated NF‐κB activation in human macrophages through interaction with the αVβ3 integrin. Molecular nutrition & food research, 56(10), 1569-1581.
Cardiff, R. D., Gumerlock, P. H., Soong, M. M., Dandekar, S., Barry, P. A., Young, L. J., & Meyers, F. J. (1988). cH-ras-1 expression in 7, 12-dimethyl benzanthracene-induced Balb/c mouse mammary hyperplasias and their tumors. Oncogene, 3(2), 205-213.
Carroll, P. A., Healy, L., Lysaght, J., Boyle, T., Reynolds, J. V., Kennedy, M. J., Pidgeon, G. & Connolly, E. M. (2011). Influence of the metabolic syndrome on leptin and leptin receptor in breast cancer. Molecular carcinogenesis, 50(8), 643-651.
Casazza, K., Page, G. P., & Fernandez, J. R. (2010). The association between the rs2234693 and rs9340799 estrogen receptor α gene polymorphisms and risk factors for cardiovascular disease: a review. Biological research for nursing, 12(1), 84-97.
Chamberlin, T., D’Amato, J. V., & Arendt, L. M. (2017). Obesity reversibly depletes the basal cell population and enhances mammary epithelial cell estrogen receptor alpha expression and progenitor activity. Breast Cancer Research, 19(1), 128.
Chan, P. C., Hsiao, F. C., Chang, H. M., Wabitsch, M., & Hsieh, P. S. (2016). Importance of adipocyte cyclooxygenase-2 and prostaglandin E2–prostaglandin E receptor 3 signaling in the development of obesity-induced adipose tissue inflammation and insulin resistance. The FASEB Journal, 30(6), 2282-2297.
Chiu, J. J., Sgagias, M. K., & Cowan, K. H. (1996). Interleukin 6 acts as a paracrine growth factor in human mammary carcinoma cell lines. Clinical cancer research, 2(1), 215-221.
Cildir, G., Akıncılar, S. C., & Tergaonkar, V. (2013). Chronic adipose tissue inflammation: all immune cells on the stage. Trends in molecular medicine, 19(8), 487-500.
Circu, M. L., & Aw, T. Y. (2012). Glutathione and modulation of cell apoptosis. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 1823(10), 1767-1777.
Circu, M. L., & Yee Aw, T. (2008). Glutathione and apoptosis. Free radical research, 42(8), 689-706.
Colditz, G. A. (1998). Relationship between estrogen levels, use of hormone replacement therapy, and breast cancer. JNCI: Journal of the National Cancer Institute, 90(11), 814-823.
Coppola, S., & Ghibelli, L. G. S. H. (2000). GSH extrusion and the mitochondrial pathway of apoptotic signalling.
Cruz-Huerta, E., Fernández-Tomé, S., Arques, M. C., Amigo, L., Recio, I., Clemente, A., & Hernández-Ledesma, B. (2015). The protective role of the Bowman-Birk protease inhibitor in soybean Lunasin digestion: the effect of released peptides on colon cancer growth. Food & function, 6(8), 2626-2635.
Curado, M. P. (2011). Breast cancer in the world: incidence and mortality. Salud pública de México, 53(5), 372-384.
D’Esposito, V., Passaretti, F., Hammarstedt, A., Liguoro, D., Terracciano, D., Molea, G., Canta, L., Miele, C., Smith, U., Beguinot, F. & Formisano, P. (2012). Adipocyte-released insulin-like growth factor-1 is regulated by glucose and fatty acids and controls breast cancer cell growth in vitro. Diabetologia, 55(10), 2811-2822.
Dai, G., Zhang, P., Ye, P., Zhang, M., Han, N., Shuai, H., & Tan, S. (2016). The Chemopreventive peptide Lunasin inhibits d-galactose-induced experimental cataract in rats. Protein and peptide letters, 23(7), 619-625.
de Lumen, B. O. (2005). Lunasin: a cancer‐preventive soy peptide. Nutrition reviews, 63(1), 16-21.
de Mejia, E. G., & Dia, V. P. (2009). Lunasin and Lunasin-like peptides inhibit inflammation through suppression of NF-κB pathway in the macrophage. Peptides, 30(12), 2388-2398.
Delort, L., Rossary, A., Farges, M. C., Vasson, M. P., & Caldefie-Chézet, F. (2015). Leptin, adipocytes and breast cancer: Focus on inflammation and anti-tumor immunity. Life sciences, 140, 37-48.
Dethlefsen, C., Højfeldt, G., & Hojman, P. (2013). The role of intratumoral and systemic IL-6 in breast cancer. Breast cancer research and treatment, 138(3), 657-664.
Dia, V. P., & de Mejia, E. G. (2010). Lunasin promotes apoptosis in human colon cancer cells by mitochondrial pathway activation and induction of nuclear clusterin expression. Cancer Letters, 295(1), 44-53.
Dia, V. P., & de Mejia, E. G. (2011). Lunasin induces apoptosis and modifies the expression of genes associated with extracellular matrix and cell adhesion in human metastatic colon cancer cells. Molecular nutrition & food research, 55(4), 623-634.
Dia, V. P., Torres, S., De Lumen, B. O., Erdman Jr, J. W., & Gonzalez De Mejia, E. (2009a). Presence of Lunasin in plasma of men after soy protein consumption. Journal of Agricultural and Food Chemistry, 57(4), 1260-1266.
Dia, V. P., Wang, W., Oh, V. L., De Lumen, B. O., & De Mejia, E. G. (2009b). Isolation, purification and characterisation of Lunasin from defatted soybean flour and in vitro evaluation of its anti-inflammatory activity. Food Chemistry, 114(1), 108-115.
Dieudonné MN, Leneveu MC, Giudicelli Y, Pecquery R. (2004). Evidence for functional estrogen receptors alpha and beta in human adipose cells: regional specificities and regulation by estrogens. Am J Physiol Cell Physiol. 286(3):C655-61.
Drori, A., Rotnemer-Golinkin, D., Zolotarov, L., & Ilan, Y. (2017). Oral administration of CardioAid and Lunasin alleviates liver damage in a high-fat diet nonalcoholic steatohepatitis model. Digestion, 96(2), 110-118.
Eguchi, A., & Feldstein, A. E. (2014). Adipocyte cell death, fatty liver disease and associated metabolic disorders. Digestive Diseases, 32(5), 579-585.
Fain, J. N., Leffler, C. W., Cowan, G. S., Buffington, C., Pouncey, L., & Bahouth, S. W. (2001). Stimulation of leptin release by arachidonic acid and prostaglandin E2 in adipose tissue from obese humans. Metabolism-Clinical and Experimental, 50(8), 921-928.
Fernández-Tomé, S., Sanchón, J., Recio, I., & Hernández-Ledesma, B. (2018). Transepithelial transport of Lunasin and derived peptides: Inhibitory effects on the gastrointestinal cancer cells viability. Journal of Food Composition and Analysis, 68, 101-110.
Fillmore, C. M., & Kuperwasser, C. (2008). Human breast cancer cell lines contain stem-like cells that self-renew, give rise to phenotypically diverse progeny and survive chemotherapy. Breast cancer research, 10(2), R25.
Fisher, D. T., Appenheimer, M. M., & Evans, S. S. (2014). The two faces of IL-6 in the tumor microenvironment. In Seminars in immunology (Vol. 26, No. 1, pp. 38-47). Academic Press.
Foryst-Ludwig, A., Clemenz, M., Hohmann, S., Hartge, M., Sprang, C., Frost, N., Krikov, M., Bhanot, S., Barrows, R., Morani, A & Gustafsson, J. Å. (2008). Metabolic actions of estrogen receptor beta (ERβ) are mediated by a negative cross-talk with PPARγ. PLoS genetics, 4(6), e1000108.
Fu, J., Hofker, M., & Wijmenga, C. (2015). Apple or pear: size and shape matter. Cell metabolism, 21(4), 507-508.
Fujisaka, S., Usui, I., Bukhari, A., Ikutani, M., Oya, T., Kanatani, Y., Tsuneyama, K., Nagai, Y., Takatsu., K., Urakaze, M., Kobayashi, M. & Kobayashi, M. (2009). Regulatory mechanisms for adipose tissue M1 and M2 macrophages in diet-induced obese mice. Diabetes, 58(11), 2574-2582.
Galvez, A. F. (2010). U.S. Patent No. 7731995B2. Washington, DC: U.S. Patent and Trademark Office.
Galvez, A. F., Chen, N., Macasieb, J., & Ben, O. (2001). Chemopreventive property of a soybean peptide (Lunasin) that binds to deacetylated histones and inhibits acetylation. Cancer research, 61(20), 7473-7478.
Garofalo, C., & Surmacz, E. (2006). Leptin and cancer. Journal of cellular physiology, 207(1), 12-22.
Gartel, A. L., & Radhakrishnan, S. K. (2005). Lost in transcription: p21 repression, mechanisms, and consequences. Cancer research, 65(10), 3980-3985.
Ghibelli, L., Fanelli, C., Rotilio, G., Lafavia, E., Coppola, S., Colussi, C., Civitareale, P. & Ciriolo, M. R. (1998). Rescue of cells from apoptosis by inhibition of active GSH extrusion. The FASEB Journal, 12(6), 479-486.
Ghobrial, I. M., Witzig, T. E., & Adjei, A. A. (2005). Targeting apoptosis pathways in cancer therapy. CA: a cancer journal for clinicians, 55(3), 178-194.
Ghosh, A. K. (2003). Regulation by Prostaglandin E2 and Histamine of Angiogenesisin Inflammatory Granulation Tissue. Yakugaku zasshi, 123(5), 295-303.
Giacinti, L., Claudio, P. P., Lopez, M., & Giordano, A. (2006). Epigenetic information and estrogen receptor alpha expression in breast cancer. The oncologist, 11(1), 1-8.
Gillespie, C., Quarshie, A., Penichet, M., & Gonzalez-Perez, R. R. (2012). Potential role of leptin signaling in DMBA-induced mammary tumors by non-responsive C57BL/6J mice fed a high-fat diet. J Carcinogene Mutagene, 3(132), 20-23.
Glynn, S. A., Prueitt, R. L., Ridnour, L. A., Boersma, B. J., Dorsey, T. M., Wink, D. A., Goodman, J.E., Yfantis, H.G., Lee, D.H. & Ambs, S. (2010). COX-2 activation is associated with Akt phosphorylation and poor survival in ER-negative, HER2-positive breast cancer. BMC cancer, 10(1), 626.
Gonzalez de Mejia, E., Vásconez, M., de Lumen, B. O., & Nelson, R. (2004). Lunasin concentration in different soybean genotypes, commercial soy protein, and isoflavone products. Journal of agricultural and food chemistry, 52(19), 5882-5887.
Gonzalez de Mejia, E., Wang, W., & Dia, V. P. (2010). Lunasin, with an arginine–glycine–aspartic acid motif, causes apoptosis to L1210 leukemia cells by activation of caspase‐3. Molecular nutrition & food research, 54(3), 406-414.
Grivennikov, S. I., Greten, F. R., & Karin, M. (2010). Immunity, inflammation, and cancer. Cell, 140(6), 883-899.
Gross, A., Newschaffer, C. J., Bolton, J. A. H., Rifai, N., & Visvanathan, K. (2013). Adipocytokines, inflammation, and breast cancer risk in postmenopausal women: a prospective study. Cancer Epidemiology and Prevention Biomarkers, cebp-1444.
Hakkak, R., Holley, A. W., MacLeod, S. L., Simpson, P. M., Fuchs, G. J., Jo, C. H., Kieber-Emmons, T. & Korourian, S. (2005). Obesity promotes 7, 12-dimethylbenz (a) anthracene-induced mammary tumor development in female zucker rats. Breast Cancer Research, 7(5), R627.
Hakkak, R., MacLeod, S., Shaaf, S., Holley, A. W., Simpson, P., Fuchs, G., Jo, C.H., Kieber-Emmons, T. & Korourian, S. (2007). Obesity increases the incidence of 7, 12-dimethylbenz (a) anthracene-induced mammary tumors in an ovariectomized Zucker rat model. International journal of oncology, 30(3), 557-563.
Harada, N., Utsumi, T., & Takagi, Y. (1993). Tissue-specific expression of the human aromatase cytochrome P-450 gene by alternative use of multiple exons 1 and promoters, and switching of tissue-specific exons 1 in carcinogenesis. Proceedings of the National Academy of Sciences, 90(23), 11312-11316.
He, Q., Gao, Z., Yin, J., Zhang, J., Yun, Z., & Ye, J. (2011). Regulation of HIF-1α activity in adipose tissue by obesity-associated factors: adipogenesis, insulin, and hypoxia. American Journal of Physiology-Endocrinology and Metabolism, 300(5), E877-E885.
Heikkilä, K., Ebrahim, S., & Lawlor, D. A. (2008). Systematic review of the association between circulating interleukin-6 (IL-6) and cancer. European journal of cancer, 44(7), 937-945.
Heinrich, P. C., Castell, J. V., & Andus, T. (1990). Interleukin-6 and the acute phase response. Biochemical journal, 265(3), 621.
Hernández-Ledesma, B., & Ben, O. (2008). Lunasin: a novel cancer preventive seed peptide. Perspectives in medicinal chemistry, 2, 75.
Hernández-Ledesma, B., Hsieh, C. C., & Ben, O. (2009a). Antioxidant and anti-inflammatory properties of cancer preventive peptide Lunasin in RAW 264.7 macrophages. Biochemical and Biophysical Research Communications, 390(3), 803-808.
Hernández-Ledesma, B., Hsieh, C. C., & Ben, O. (2009b). Lunasin and Bowman-Birk protease inhibitor (BBI) in US commercial soy foods. Food Chemistry, 115(2), 574-580.
Hernández‐Ledesma, B., Hsieh, C. C., & de Lumen, B. O. (2011a). Relationship between Lunasin's sequence and its inhibitory activity of histones H3 and H4 acetylation. Molecular nutrition & food research, 55(7), 989-998.
Hernández-Ledesma, B., Hsieh, C. C., Dia, V., de Mejia, E. G., & Ben, O. (2011b). Lunasin, a Cancer Preventive Seed Peptide. In Soybean and Health. InTech.
Hicklin, D. J., & Ellis, L. M. (2005). Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. Journal of clinical oncology, 23(5), 1011-1027.
Hopp, T. A., Weiss, H. L., Parra, I. S., Cui, Y., Osborne, C. K., & Fuqua, S. A. (2004). Low levels of estrogen receptor β protein predict resistance to tamoxifen therapy in breast cancer. Clinical Cancer Research, 10(22), 7490-7499.
Howe, L. R., Subbaramaiah, K., Brown, A. M., & Dannenberg, A. J. (2001). Cyclooxygenase-2: a target for the prevention and treatment of breast cancer. Endocrine-related cancer, 8(2), 97-114.
Hsiao, K. Y., Lin, S. C., Wu, M. H., & Tsai, S. J. (2015). Pathological functions of hypoxia in endometriosis. Front Biosci (Elite Ed), 7, 309-321.
Hsieh, C. C., Chou, M. J., & Wang, C. H. (2017a). Lunasin attenuates obesity-related inflammation in RAW264. 7 cells and 3T3-L1 adipocytes by inhibiting inflammatory cytokine production. PloS one, 12(2), e0171969.
Hsieh, C. C., Hernández-Ledesma, B., & Ben, O. (2010a). Lunasin, a novel seed peptide, sensitizes human breast cancer MDA-MB-231 cells to aspirin-arrested cell cycle and induced apoptosis. Chemico-Biological Interactions, 186(2), 127-134.
Hsieh, C. C., Hernández-Ledesma, B., & Ben, O. (2011). Lunasin–Aspirin Combination Against NIH/3T3 Cells Transformation Induced by Chemical Carcinogens. Plant Foods for Human Nutrition, 66(2), 107-113.
Hsieh, C. C., Hernández‐Ledesma, B., & De Lumen, B. O. (2010b). Soybean Peptide Lunasin Suppresses In Vitro and In Vivo 7, 12‐Dimethylbenz [a] anthracene‐Induced Tumorigenesis. Journal of Food Science, 75(9).
Hsieh, C. C., Hernández-Ledesma, B., Jeong, H. J., Park, J. H., & Ben, O. (2010c). Complementary roles in cancer prevention: protease inhibitor makes the cancer preventive peptide Lunasin bioavailable. PloS one, 5(1), e8890.
Hsieh, C. C., Martínez‐Villaluenga, C., de Lumen, B. O., & Hernández‐Ledesma, B. (2017b). Updating the research on the chemopreventive and therapeutic role of peptide Lunasin. Journal of the Science of Food and Agriculture.
Hsieh, C. C., Peng, S. H., & Chou, M. J. (2017c). Obesity enhances carcinogen 7, 12-Dimethylbenz [a] anthracene-induced tumorigenesis in vitro and in vivo. Food and Chemical Toxicology, 110, 156-164.
Hsieh, C. C., Peng, S. H., (2018) The effects of lunasin on the growth of obesity-mediated MCF-7 and MDA-MB-231 human breast cancer cells. Manuscript.
Hsieh, C. C., Wang, C. H., & Huang, Y. S. (2016). Lunasin attenuates obesity-associated metastasis of 4T1 breast cancer cell through anti-inflammatory property. International journal of molecular sciences, 17(12), 2109.
Hsieh, P. S., Jin, J. S., Chiang, C. F., Chan, P. C., Chen, C. H., & Shih, K. C. (2009). COX‐2‐mediated inflammation in fat is crucial for obesity‐linked insulin resistance and fatty liver. Obesity, 17(6), 1150-1157.
Huang, B., Omoto, Y., Iwase, H., Yamashita, H., Toyama, T., Coombes, R. C., Filipovic, A., Warner, M. & Gustafsson, J. Å. (2014). Differential expression of estrogen receptor α, β1, and β2 in lobular and ductal breast cancer. Proceedings of the National Academy of Sciences, 111(5), 1933-1938.
Huang, L. E., Gu, J., Schau, M., & Bunn, H. F. (1998). Regulation of hypoxia-inducible factor 1α is mediated by an O2-dependent degradation domain via the ubiquitin-proteasome pathway. Proceedings of the National Academy of Sciences, 95(14), 7987-7992.
Huang, L., Li, A., Liao, G., Yang, F., Yang, J., Chen, X., & Jiang, X. (2017). Curcumol triggers apoptosis of p53 mutant triple-negative human breast cancer MDA-MB 231 cells via activation of p73 and PUMA. Oncology letters, 14(1), 1080-1088.
Huang, Z., Hankinson, S. E., Colditz, G. A., Stampfer, M. J., Hunter, D. J., Manson, J. E., Hennekens, C.H., Ronser, B., Speizer, F.E. & Willett, W. C. (1997). Dual effects of weight and weight gain on breast cancer risk. Jama, 278(17), 1407-1411.
Hubatsch, I., Ragnarsson, E. G., & Artursson, P. (2007). Determination of drug permeability and prediction of drug absorption in Caco-2 monolayers. Nature protocols, 2(9), 2111.
Hughes, R., Timmermans, P., & Schrey, M. P. (1996). Regulation of arachidonic acid metabolism, aromatase activity and growth in human breast cancer cells by interleukin‐1β and phorbol ester: Dissociation of a mediatory role for prostaglandin E2 in the autocrine control of cell function. International journal of cancer, 67(5), 684-689.
Hugo, H. J., Saunders, C., Ramsay, R. G., & Thompson, E. W. (2015). New insights on COX-2 in chronic inflammation driving breast cancer growth and metastasis. Journal of mammary gland biology and neoplasia, 20(3-4), 109-119.
Huh, J. Y., Jung, I., Piao, L., Ha, H., & Chung, M. H. (2017). 8-Hydroxy-2-deoxyguanosine ameliorates high-fat diet-induced insulin resistance and adipocyte dysfunction in mice. Biochemical and biophysical research communications, 491(4), 890-896.
Hui, L., Zheng, Y., Yan, Y., Bargonetti, J., & Foster, D. A. (2006). Mutant p53 in MDA-MB-231 breast cancer cells is stabilized by elevated phospholipase D activity and contributes to survival signals generated by phospholipase D. Oncogene, 25(55), 7305.
Iliopoulos, D., Hirsch, H. A., Wang, G., & Struhl, K. (2011). Inducible formation of breast cancer stem cells and their dynamic equilibrium with non-stem cancer cells via IL6 secretion. Proceedings of the National Academy of Sciences, 201018898.
Irigaray, P., Newby, J. A., Clapp, R., Hardell, L., Howard, V., Montagnier, L., Epstein, S. & Belpomme, D. (2007). Lifestyle-related factors and environmental agents causing cancer: an overview. Biomedicine & Pharmacotherapy, 61(10), 640-658.
Isobe, T., Aoyagi, K., Koufuji, K., Shirouzu, K., Kawahara, A., Taira, T., & Kage, M. (2013). Clinicopathological significance of hypoxia-inducible factor-1 alpha (HIF-1α) expression in gastric cancer. International journal of clinical oncology, 18(2), 293-304.
Iwase, H., Zhang, Z., Omoto, Y., Sugiura, H., Yamashita, H., Toyama, T., Iwata, H. & Kobayashi, S. (2003). Clinical significance of the expression of estrogen receptors α and β for endocrine therapy of breast cancer. Cancer chemotherapy and pharmacology, 52(1), 34-38.
Iyengar, N. M., Brown, K. A., Zhou, X. K., Gucalp, A., Subbaramaiah, K., Giri, D. D., Zahid, H., Bhardwaj, P., Wendel, N.K., Falcone, D.J., Wang, H., Williams, S., Pollak, M., Morrow, M., Hudis, C.A., & Wang, H. (2017). Metabolic obesity, adipose inflammation and elevated breast aromatase in women with normal body mass index. Cancer Prevention Research, 10(4), 235-243.
Iyengar, N. M., Hudis, C. A., & Dannenberg, A. J. (2013). Obesity and inflammation: new insights into breast cancer development and progression. In American Society of Clinical Oncology educational book/ASCO. American Society of Clinical Oncology. Meeting (Vol. 33, p. 46). NIH Public Access.
Iyengar, P., Combs, T. P., Shah, S. J., Gouon-Evans, V., Pollard, J. W., Albanese, C., Flanagan, L., Tenniswood, M. P., Guha, C., Lisanti, M. P., Pestell, R. G. & Scherer, M. E. (2003). Adipocyte-secreted factors synergistically promote mammary tumorigenesis through induction of anti-apoptotic transcriptional programs and proto-oncogene stabilization. Oncogene, 22(41), 6408-6423.
Jana, D., Sarkar, D. K., Ganguly, S., Saha, S., Sa, G., Manna, A. K., Banerjee, A. & Mandal, S. (2014). Role of cyclooxygenase 2 (COX-2) in prognosis of breast cancer. Indian journal of surgical oncology, 5(1), 59-65.
Jardé, T., Caldefie-Chézet, F., Damez, M., Mishellany, F., Penault-Llorca, F., Guillot, J., & Vasson, M. P. (2008). Leptin and leptin receptor involvement in cancer development: a study on human primary breast carcinoma. Oncology reports, 19(4), 905-911.
Jardé, T., Perrier, S., Vasson, M. P., & Caldefie-Chézet, F. (2011). Molecular mechanisms of leptin and adiponectin in breast cancer. European journal of cancer, 47(1), 33-43.
Jeong, H. J., Jeong, J. B., Hsieh, C. C., Hernández-Ledesma, B., & de Lumen, B. O. (2010a). Lunasin is prevalent in barley and is bioavailable and bioactive in in vivo and in vitro studies. Nutrition and cancer, 62(8), 1113-1119.
Jeong, H. J., Jeong, J. B., Kim, D. S., Park, J. H., Lee, J. B., Kweon, D. H., ... & Ben, O. (2007a). The cancer preventive peptide Lunasin from wheat inhibits core histone acetylation. Cancer letters, 255(1), 42-48.
Jeong, J. B., Ben, O., & Jeong, H. J. (2010b). Lunasin peptide purified from Solanum nigrum L. protects DNA from oxidative damage by suppressing the generation of hydroxyl radical via blocking fenton reaction. Cancer Letters, 293(1), 58-64.
Jeong, J. B., Jeong, H. J., Park, J. H., Lee, S. H., Lee, J. R., Lee, H. K., ... & De Lumen, B. O. (2007b). Cancer-preventive peptide Lunasin from Solanum nigrum L. inhibits acetylation of core histones H3 and H4 and phosphorylation of retinoblastoma protein (Rb). Journal of agricultural and food chemistry, 55(26), 10707-10713.
Jia, S., Zhang, S., Yuan, H., & Chen, N. (2015). Lunasin inhibits cell proliferation via apoptosis and reduces the production of proinflammatory cytokines in cultured rheumatoid arthritis synovial fibroblasts. BioMed research international, 2015.
Jiang, Q., Pan, Y., Cheng, Y., Li, H., Liu, D., & Li, H. (2016). Lunasin suppresses the migration and invasion of breast cancer cells by inhibiting matrix metalloproteinase-2/-9 via the FAK/Akt/ERK and NF-κB signaling pathways. Oncology reports, 36(1), 253-262.
Jin, Y., Deng, Z., Tipoe, G. L., & White, F. H. (1998). Relationship between the mRNA transcriptions of bFGF and KGF in the carcinogenesis of oral mucosa. Hua xi kou qiang yi xue za zhi= Huaxi kouqiang yixue zazhi= West China journal of stomatology, 16(1), 23-25.
Kant, A. K., & Graubard, B. I. (2006). Secular trends in patterns of self-reported food consumption of adult Americans: NHANES 1971-1975 to NHANES 1999–2002. The American journal of clinical nutrition, 84(5), 1215-1223.
Kawanishi, N., Niihara, H., Mizokami, T., Yada, K., & Suzuki, K. (2015). Exercise training attenuates neutrophil infiltration and elastase expression in adipose tissue of high‐fat‐diet‐induced obese mice. Physiological reports, 3(9), e12534.
Kelly, P. M. A., Davison, R. S., Bliss, E., & McGee, J. D. (1988). Macrophages in human breast disease: a quantitative immunohistochemical study. British journal of cancer, 57(2), 174.
Khan, S., Shukla, S., Sinha, S., & Meeran, S. M. (2013). Role of adipokines and cytokines in obesity-associated breast cancer: therapeutic targets. Cytokine & growth factor reviews, 24(6), 503-513.
Kimura, A., & Kishimoto, T. (2010). IL‐6: regulator of Treg/Th17 balance. European journal of immunology, 40(7), 1830-1835.
Korn, T., Bettelli, E., Oukka, M., & Kuchroo, V. K. (2009). IL-17 and Th17 Cells. Annual review of immunology, 27, 485-517.
Lam, Y. Y., Ha, C. W., Campbell, C. R., Mitchell, A. J., Dinudom, A., Oscarsson, J., Cook, D. I., Hunt, N. H., Caterson, I. D., Holmes, A. J. & Storlien, L. H. (2012). Increased gut permeability and microbiota change associate with mesenteric fat inflammation and metabolic dysfunction in diet-induced obese mice. PloS one, 7(3), e34233.
Lam, Y., Galvez, A., & de Lumen, B. O. (2003). Lunasin™ suppresses E1A-mediated transformation of mammalian cells but does not inhibit growth of immortalized and established cancer cell lines. Nutrition and cancer, 47(1), 88-94.
Lamas, B., Nachat‐Kappes, R., Goncalves‐Mendes, N., Mishellany, F., Rossary, A., Vasson, M. P., & Farges, M. C. (2015). Dietary fat without body weight gain increases in vivo MCF‐7 human breast cancer cell growth and decreases natural killer cell cytotoxicity. Molecular carcinogenesis, 54(1), 58-71.
Lee, Y., Jung, W. H., & Koo, J. S. (2015). Adipocytes can induce epithelial-mesenchymal transition in breast cancer cells. Breast cancer research and treatment, 153(2), 323-335.
Leslie, K., Gao, S. P., Berishaj, M., Podsypanina, K., Ho, H., Ivashkiv, L., & Bromberg, J. (2010). Differential interleukin-6/Stat3 signaling as a function of cellular context mediates Ras-induced transformation. Breast Cancer Research, 12(5), R80.
Li, Q., Hata, A., Kosugi, C., Kataoka, N., & Funaki, M. (2010). The density of extracellular matrix proteins regulates inflammation and insulin signaling in adipocytes. FEBS letters, 584(19), 4145-4150.
Li, T., Zhang, C., DiNG, Y., ZHAi, W., LiU, K., Bu, F., Tu, T., Sun, L., Zhu, W., Zhou, F., Qi, W., Hu, J., Chen, H. & Sun, X. (2015). Umbilical cord-derived mesenchymal stem cells promote proliferation and migration in MCF-7 and MDA-MB-231 breast cancer cells through activation of the ERK pathway. Oncology reports, 34(3), 1469-1477.
Ligibel, J. A., & Strickler, H. D. (2013). Obesity and its impact on breast cancer: tumor incidence, recurrence, survival, and possible interventions. Am Soc Clin Oncol Educ Book, 2013, 52-59.
Liu, F., & Yu, C. (2014). IL-8 promote carcinogenesis of primary epithelial cells from familial adenomatous polyposis. Cell biochemistry and biophysics, 70(3), 1765-1771.
Liu, X., Zhao, W., Wang, W., Lin, S., & Yang, L. (2017). Puerarin suppresses LPS-induced breast cancer cell migration, invasion and adhesion by blockage NF-κB and Erk pathway. Biomedicine & Pharmacotherapy, 92, 429-436.
Lizcano, F., & Guzmán, G. (2014). Estrogen deficiency and the origin of obesity during menopause. BioMed research international, 2014.
Lu, H., Shi, J. X., Zhang, D. M., Wang, H. D., Hang, C. H., Chen, H. L., & Yin, H. X. (2009). Inhibition of hemolysate-induced iNOS and COX-2 expression by genistein through suppression of NF-кB activation in primary astrocytes. Journal of the neurological sciences, 278(1), 91-95.
Lukas, J., Bartkova, J., & Bartek, J. (1996). Convergence of mitogenic signalling cascades from diverse classes of receptors at the cyclin D-cyclin-dependent kinase-pRb-controlled G1 checkpoint. Molecular and cellular biology, 16(12), 6917-6925.
Lumen, B. O. (2005). Lunasin: A Cancer‐Preventive Soy Peptide. Nutrition reviews, 63(1), 16-21.
Macciò, A., & Madeddu, C. (2011). Obesity, inflammation, and postmenopausal breast cancer: therapeutic implications. The Scientific World Journal, 11, 2020-2036.
Macciò, A., Madeddu, C., Gramignano, G., Mulas, C., Floris, C., Massa, D., Astara, G., Chessa, P. & Mantovani, G. (2010). Correlation of body mass index and leptin with tumor size and stage of disease in hormone-dependent postmenopausal breast cancer: preliminary results and therapeutic implications. Journal of molecular medicine, 88(7), 677-686.
McCawley, L. J., & Matrisian, L. M. (2000). Matrix metalloproteinases: multifunctional contributors to tumor progression. Molecular medicine today, 6(4), 149-156.
McConnell, E. J., Devapatla, B., Yaddanapudi, K., & Davis, K. R. (2015). The soybean-derived peptide Lunasin inhibits non-small cell lung cancer cell proliferation by suppressing phosphorylation of the retinoblastoma protein. Oncotarget, 6(7), 4649.
McMichael-Phillips, D. F., Harding, C., Morton, M., Roberts, S. A., Howell, A., Potten, C. S., & Bundred, N. J. (1998). Effects of soy-protein supplementation on epithelial proliferation in the histologically normal human breast. The American journal of clinical nutrition, 68(6), 1431S-1435S.
Meister, A., & Anderson, M. E. (1983). Glutathione. Annual review of biochemistry, 52(1), 711-760.
Messina, M., & Gleason, C. (2016). Evaluation of the potential antidepressant effects of soybean isoflavones. Menopause, 23(12), 1348-1360.
Miller, W. R., Anderson, T. J., & Jack, W. J. L. (1990). Relationship between tumour aromatase activity, tumour characteristics and response to therapy. The Journal of steroid biochemistry and molecular biology, 37(6), 1055-1059.
Miller, W. R., Mullen, P., Sourdaine, P., Watson, C., Dixon, J. M., & Telford, J. (1997). Regulation of aromatase activity within the breast. The Journal of steroid biochemistry and molecular biology, 61(3-6), 193-202.
Miyoshi, Y., Funahashi, T., Kihara, S., Taguchi, T., Tamaki, Y., Matsuzawa, Y., & Noguchi, S. (2003). Association of serum adiponectin levels with breast cancer risk. Clinical Cancer Research, 9(15), 5699-5704.
Mizejewski, G. J. (1999). Role of integrins in cancer: survey of expression patterns. Proceedings of the Society for Experimental Biology and Medicine, 222(2), 124-138.
Montales, M. T. E., Rahal, O. M., Kang, J., Rogers, T. J., Prior, R. L., Wu, X., & Simmen, R. C. (2012). Repression of mammosphere formation of human breast cancer cells by soy isoflavone genistein and blueberry polyphenolic acids suggests diet-mediated targeting of cancer stem-like/progenitor cells. Carcinogenesis, 33(3), 652-660.
Moy, I., Lin, Z., Rademaker, A. W., Reierstad, S., Khan, S. A., & Bulun, S. E. (2013). Expression of estrogen-related gene markers in breast cancer tissue predicts aromatase inhibitor responsiveness. PloS one, 8(11), e77543.
Murano, I., Barbatelli, G., Parisani, V., Latini, C., Muzzonigro, G., Castellucci, M., & Cinti, S. (2008). Dead adipocytes, detected as crown-like structures, are prevalent in visceral fat depots of genetically obese mice. Journal of lipid research, 49(7), 1562-1568.
Nadal‐Serrano, M., Sastre‐Serra, J., Pons, D. G., Miró, A. M., Oliver, J., & Roca, P. (2012). The ERalpha/ERbeta ratio determines oxidative stress in breast cancer cell lines in response to 17Beta‐estradiol. Journal of cellular biochemistry, 113(10), 3178-3185.
Nakajima, S., Koh, V., Kua, L. F., So, J., Davide, L., Lim, K. S., Petersen, S. H., Yong, W. P., Shabbir, A. & Kono, K. (2016). Accumulation of CD11c+ CD163+ adipose tissue macrophages through upregulation of intracellular 11β-HSD1 in human obesity. The Journal of Immunology, 197(9), 3735-3745.
National Institutes of Health. Obesity Education Initiative Expert Panel on the Identification, Evaluation, and Treatment of Obesity in Adults (US, 1998).
Nelson, A. R., Fingleton, B., Rothenberg, M. L., & Matrisian, L. M. (2000). Matrix metalloproteinases: biologic activity and clinical implications. Journal of clinical oncology, 18(5), 1135-1135.
Nishida, N., Yano, H., Nishida, T., Kamura, T., & Kojiro, M. (2006). Angiogenesis in cancer. Vascular health and risk management, 2(3), 213.
Ntambi, J. M., & Young-Cheul, K. (2000). Adipocyte differentiation and gene expression. The Journal of nutrition, 130(12), 3122S-3126S.
Okada, M., Kitahara, M., Kishimoto, S., Matsuda, T., Hirano, T., & Kishimoto, T. (1988). IL-6/BSF-2 functions as a killer helper factor in the in vitro induction of cytotoxic T cells. The Journal of Immunology, 141(5), 1543-1549.
Okumura, M., Yamamoto, M., Sakuma, H., Kojima, T., Maruyama, T., Jamali, M., Cooper, D. R. & Yasuda, K. (2002). Leptin and high glucose stimulate cell proliferation in MCF-7 human breast cancer cells: reciprocal involvement of PKC-α and PPAR expression. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 1592(2), 107-116.
Olea, E., Agapito, M. T., Gallego-Martin, T., Rocher, A., Gomez-Niño, A., Obeso, A., Gonzalez, C. & Yubero, S. (2014). Intermittent hypoxia and diet-induced obesity: effects on oxidative status, sympathetic tone, plasma glucose and insulin levels, and arterial pressure. Journal of Applied Physiology, 117(7), 706-719.
Ollberding, N. J., Kim, Y., Shvetsov, Y. B., Wilkens, L. R., Franke, A. A., Cooney, R. V., Maskarinec, G., Hernandez, B. Y., Henderson, B. E., Marchand, L. L., Kolonel, L. N. & Kolonel, L. N. (2013). Prediagnostic leptin, adiponectin, C-reactive protein, and the risk of postmenopausal breast cancer. Cancer prevention research, 6(3), 188-195.
Omoto, Y., Inoue, S., Ogawa, S., Toyama, T., Yamashita, H., Muramatsu, M., Kobayashi, S. & Iwase, H. (2001). Clinical value of the wild-type estrogen receptor β expression in breast cancer. Cancer letters, 163(2), 207-212.
Orsulic, S., Huber, O., Aberle, H., Arnold, S., & Kemler, R. (1999). E-cadherin binding prevents beta-catenin nuclear localization and beta-catenin/LEF-1-mediated transactivation. Journal of cell science, 112(8), 1237-1245.
Ouchi, N., Kihara, S., Arita, Y., Nishida, M., Matsuyama, A., Okamoto, Y., Ishigami, M., Kuriyama, H., Kishida, K., Nishizawa, H., Hotta, K., Muraguchi, M., Ohmoto, Y., Yamashita, S>, Funahashi, T. & Matsuzawa, Y. (2001). Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages. Circulation, 103(8), 1057-1063.
Pabona, J. M. P., Dave, B., Su, Y., Montales, M. T. E., Ben, O., De Mejia, E. G., Rahal, O. M. & Simmen, R. C. (2013). The soybean peptide Lunasin promotes apoptosis of mammary epithelial cells via induction of tumor suppressor PTEN: similarities and distinct actions from soy isoflavone genistein. Genes & nutrition, 8(1), 79-90.
Papachristou, G. I. (2008). Prediction of severe acute pancreatitis: current knowledge and novel insights. World journal of gastroenterology: WJG, 14(41), 6273.
Park, J. H., Jeong, H. J., & Lumen, B. O. D. (2007a). In vitro digestibility of the cancer-preventive soy peptides Lunasin and BBI. Journal of agricultural and food chemistry, 55(26), 10703-10706.
Park, J. H., Jeong, J. B., De Lumen, B. O., & Jeong, H. J. (2007b). The Anticancer Properties of Lunasin Peptide from Aged Callus Induced by the Soybean Tissue Culture. Korean Journal of Plant Resources, 20(6), 518-523.
Park, J., Morley, T. S., Kim, M., Clegg, D. J., & Scherer, P. E. (2014). Obesity and cancer [mdash] mechanisms underlying tumour progression and recurrence. Nature Reviews Endocrinology, 10(8), 455-465.
Park, W. C., Seo, I., Kim, S. H., Lee, Y. J., & Ahn, S. V. (2017). Association between Resting Heart Rate and Inflammatory Markers (White Blood Cell Count and High-Sensitivity C-Reactive Protein) in Healthy Korean People. Korean journal of family medicine, 38(1), 8-13.
Parrales, A., & Iwakuma, T. (2015). Targeting oncogenic mutant p53 for cancer therapy. Frontiers in oncology, 5, 288.
Pedersen, B. K. (2006). The anti-inflammatory effect of exercise: its role in diabetes and cardiovascular disease control. Essays in biochemistry, 42, 105-117.
Phytoestrogen‐mediated inhibition of prolifera-
Phytoestrogen‐mediated inhibition of prolifera-
Pini, M., Castellanos, K. J., Rhodes, D. H., & Fantuzzi, G. (2013). Obesity and IL-6 interact in modulating the response to endotoxemia in mice. Cytokine, 61(1), 71-77.
Pons, D. G., Nadal‐Serrano, M., Blanquer‐Rossello, M. M., Sastre‐Serra, J., Oliver, J., & Roca, P. (2014). Genistein modulates proliferation and mitochondrial functionality in breast cancer cells depending on ERalpha/ERbeta ratio. Journal of cellular biochemistry, 115(5), 949-958.
Prentice, A. M. (2006). The emerging epidemic of obesity in developing countries. International journal of epidemiology, 35(1), 93-99.
Prentice, A. M., & Jebb, S. A. (1995). Obesity in Britain: gluttony or sloth?. BMJ: British Medical Journal, 311(7002), 437.
Purohit, A., Ghilchik, M. W., Duncan, L., Wang, D. Y., Singh, A., Walker, M. M., & Reed, M. J. (1995). Aromatase activity and interleukin-6 production by normal and malignant breast tissues. The Journal of Clinical Endocrinology & Metabolism, 80(10), 3052-3058.
Purohit, A., Singh, A., Ghilchik, M. W., & Reed, M. J. (1999). Inhibition of tumor necrosis factor α-stimulated aromatase activity by microtubule-stabilizing agents, paclitaxel and 2-methoxyestradiol. Biochemical and biophysical research communications, 261(1), 214-217.
Qiu, M., Peng, Q., Jiang, I., Carroll, C., Han, G., Rymer, I., Lippincott, J., Zachwieja, J., Gajiwala, K., Kraynov, E., Thibault, S., Stone, D., Gao, Y., Sofia, S., Gallo, J., Li G., Yang, J., Li, K. & Wei, P. (2013). Specific inhibition of Notch1 signaling enhances the antitumor efficacy of chemotherapy in triple negative breast cancer through reduction of cancer stem cells. Cancer letters, 328(2), 261-270.
Rahimi, N. (2012). The ubiquitin-proteasome system meets angiogenesis. Molecular cancer therapeutics, 11(3), 538-548.
Ray, I., Mahata, S. K., & De, R. K. (2016). Obesity: an immunometabolic perspective. Frontiers in endocrinology, 7.
Recchia, A. G., De Francesco, E. M., Vivacqua, A., Sisci, D., Panno, M. L., Andò, S., & Maggiolini, M. (2011). The G protein-coupled receptor 30 is up-regulated by hypoxia-inducible factor-1α (HIF-1α) in breast cancer cells and cardiomyocytes. Journal of Biological Chemistry, 286(12), 10773-10782.
Reed, D. J. (1990). Glutathione: toxicological implications. Annual Review of Pharmacology and Toxicology, 30(1), 603-631.
Reed, M. J., & Purohit, A. (2001). Aromatase regulation and breast cancer. Clinical endocrinology, 54(5), 563-571.
Renehan, A. G., Tyson, M., Egger, M., Heller, R. F., & Zwahlen, M. (2008). Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. The Lancet, 371(9612), 569-578.
Ristimäki, A., Sivula, A., Lundin, J., Lundin, M., Salminen, T., Haglund, C., Joensuu, H. & Isola, J. (2002). Prognostic significance of elevated cyclooxygenase-2 expression in breast cancer. Cancer research, 62(3), 632-635.
Rom-Jurek, E. M., Kirchhammer, N., Ugocsai, P., Ortmann, O., Wege, A. K., & Brockhoff, G. (2018). Regulation of Programmed Death Ligand 1 (PD-L1) Expression in Breast Cancer Cell Lines In Vitro and in Immunodeficient and Humanized Tumor Mice. International journal of molecular sciences, 19(2), 563.
Ruoslahti, E., & Pierschbacher, M. D. (1987). New perspectives in cell adhesion: RGD and integrins. Science, 238(4826), 491-497.
Salven, P., Lymboussaki, A., Heikkilä, P., Jääskela-Saari, H., Enholm, B., Aase, K., Euler, G. V., Eriksson, U., Alitalo, K. & Joensuu, H. (1998). Vascular endothelial growth factors VEGF-B and VEGF-C are expressed in human tumors. The American journal of pathology, 153(1), 103-108.
Sastre-Serra, J., Nadal-Serrano, M., Pons, D. G., Valle, A., Oliver, J., & Roca, P. (2012). The effects of 17β-estradiol on mitochondrial biogenesis and function in breast cancer cell lines are dependent on the ERα/ERβ ratio. Cellular Physiology and Biochemistry, 29(1-2), 261-268.
Sastre-Serra, J., Valle, A., Garau, I., Oliver, J., & Roca, P. (2010). Estrogen down-regulates uncoupling proteins and increases oxidative stress in breast cancer. Free Radical Biology and Medicine, 48(4), 506-512.
Scheele, C., Nielsen, S., Kelly, M., Broholm, C., Nielsen, A. R., Taudorf, S., Pedersen, M., Fischer, C.P. & Pedersen, B. K. (2012). Satellite cells derived from obese humans with type 2 diabetes and differentiated into myocytes in vitro exhibit abnormal response to IL-6. PloS one, 7(6), e39657.
Selander, K. S., Li, L., Watson, L., Merrell, M., Dahmen, H., Heinrich, P. C., Müller-Newen, G. & Harris, K. W. (2004). Inhibition of gp130 signaling in breast cancer blocks constitutive activation of Stat3 and inhibits in vivo malignancy. Cancer research, 64(19), 6924-6933.
Shanmugalingam, T., Bosco, C., Ridley, A. J., & Van Hemelrijck, M. (2016). Is there a role for IGF‐1 in the development of second primary cancers?. Cancer medicine, 5(11), 3353-3367.
Sharma, M., Mohapatra, J., Argade, A., Deshpande, S. S., Shah, G. B., Chatterjee, A., & Jain, M. R. (2014). Chemopreventive effect of a novel, selective TACE inhibitor on DMBA-and TPA-induced skin carcinogenesis. Immunopharmacology and immunotoxicology, 36(4), 282-289.
Shpilberg, Y., Connor, M. K., & Riddell, M. C. (2015). The direct and indirect effects of corticosterone and primary adipose tissue on MCF7 breast cancer cell cycle progression. Hormone molecular biology and clinical investigation, 22(2), 91-100.
Singh, A., Purohit, A., Ghilchik, M. W., & Reed, M. J. (1999). The regulation of aromatase activity in breast fibroblasts: the role of interleukin-6 and prostaglandin E2. Endocrine-Related Cancer, 6(2), 139-147.
Singh, P., & Bisetty, K. (2012). A molecular dynamics study of Lunasin. South African Journal of Chemistry, 65(1), 115-124.
Strissel, K. J., Stancheva, Z., Miyoshi, H., Perfield, J. W., DeFuria, J., Jick, Z., Greemberg, A. S. & Obin, M. S. (2007). Adipocyte death, adipose tissue remodeling, and obesity complications. Diabetes, 56(12), 2910-2918.
Su, Y., & Simmen, R. C. (2008). Soy isoflavone genistein upregulates epithelial adhesion molecule E-cadherin expression and attenuates β-catenin signaling in mammary epithelial cells. Carcinogenesis, 30(2), 331-339.
Subbaramaiah, K., Morris, P. G., Zhou, X. K., Morrow, M., Du, B., Giri, D., Kopelovich, L., Hudis, C. A. & Dannenberg, A. J. (2012). Increased levels of COX-2 and prostaglandin E2 contribute to elevated aromatase expression in inflamed breast tissue of obese women. Cancer discovery, 2(4), 356-365.
Sun, L., Yu, D. H., Sun, S. Y., Zhuo, S. C., Cao, S. S., & Wei, L. (2014). Expressions of ER, PR, HER-2, COX-2, and VEGF in primary and relapsed/metastatic breast cancers. Cell biochemistry and biophysics, 68(3), 511-516.
Takemura, H., Itoh, T., Yamamoto, K., Sakakibara, H., & Shimoi, K. (2010). Selective inhibition of methoxyflavonoids on human CYP1B1 activity. Bioorganic & medicinal chemistry, 18(17), 6310-6315.
Tanaka, T., Narazaki, M., & Kishimoto, T. (2014). IL-6 in inflammation, immunity, and disease. Cold Spring Harbor perspectives in biology, a016295.
Tanimoto, K., Makino, Y., Pereira, T., & Poellinger, L. (2000). Mechanism of regulation of the hypoxia‐inducible factor‐1α by the von Hippel‐Lindau tumor suppressor protein. The EMBO journal, 19(16), 4298-4309.
Tao, K., Fang, M., Alroy, J., & Sahagian, G. G. (2008). Imagable 4T1 model for the study of late stage breast cancer. BMC cancer, 8(1), 228.
Teng, F. Y., Wu, S. K., Hsia, Y. Y., Kao, W. B., & Hsieh, Y. D. (2006). Modulation of inflammation, apoptosis, and oncogenesis by the nuclear transcription factor, NF-kappaB. Chinese Dental Journal, 25(1), 12.
tion of the human T47D breast cancer cells depends on the ERalpha/ERbeta
tion of the human T47D breast cancer cells depends on the ERalpha/ERbeta
Torre, L. A., Bray, F., Siegel, R. L., Ferlay, J., Lortet‐Tieulent, J., & Jemal, A. (2015). Global cancer statistics, 2012. CA: a cancer journal for clinicians, 65(2), 87-108.
Trastour, C., Benizri, E., Ettore, F., Ramaioli, A., Chamorey, E., Pouysségur, J., & Berra, E. (2007). HIF‐1α and CA IX staining in invasive breast carcinomas: Prognosis and treatment outcome. International journal of cancer, 120(7), 1451-1458.
Trayhurn, P. (2013). Hypoxia and adipose tissue function and dysfunction in obesity. Physiological reviews, 93(1), 1-21.
Treeck, O., Juhasz-Boess, I., Lattrich, C., Horn, F., Goerse, R., & Ortmann, O. (2008). Effects of exon-deleted estrogen receptor β transcript variants on growth, apoptosis and gene expression of human breast cancer cell lines. Breast cancer research and treatment, 110(3), 507-520.
Uifălean, A., Schneider, S., Gierok, P., Ionescu, C., Iuga, C. A., & Lalk, M. (2016). The impact of soy isoflavones on MCF-7 and MDA-MB-231 breast cancer cells using a global metabolomic approach. International journal of molecular sciences, 17(9), 1443.
Uifălean, A., Schneider, S., Ionescu, C., Lalk, M., & Iuga, C. A. (2015). Soy isoflavones and breast cancer cell lines: Molecular mechanisms and future perspectives. Molecules, 21(1), 13.
Ullah, M. F., Ahmad, A., Zubair, H., Khan, H. Y., Wang, Z., Sarkar, F. H., & Hadi, S. M. (2011). Soy isoflavone genistein induces cell death in breast cancer cells through mobilization of endogenous copper ions and generation of reactive oxygen species. Molecular nutrition & food research, 55(4), 553-559.
Wan, X., Liu, H., Sun, Y., Zhang, J., Chen, X., & Chen, N. (2017). Lunasin: A promising polypeptide for the prevention and treatment of cancer. Oncology Letters, 13(6), 3997-4001.
Wang, J., Huang, J., Wang, L., Chen, C., Yang, D., Jin, M., ... & Song, Y. (2017). Urban particulate matter triggers lung inflammation via the ROS-MAPK-NF-κB signaling pathway. Journal of thoracic disease, 9(11), 4398.
Wang, S. W., Liu, S. C., Sun, H. L., Huang, T. Y., Chan, C. H., Yang, C. Y., Yeh, H. I., Huang, Y. L., Chou, W. Y. Lin, Y. M. & Tang, C. H. (2014). CCL5/CCR5 axis induces vascular endothelial growth factor-mediated tumor angiogenesis in human osteosarcoma microenvironment. Carcinogenesis, 36(1), 104-114.
Wang, X., Buechler, N. L., Yoza, B. K., McCall, C. E., & Vachharajani, V. (2016). Adiponectin treatment attenuates inflammatory response during early sepsis in obese mice. Journal of inflammation research, 9, 167.
Weisberg, S. P., McCann, D., Desai, M., Rosenbaum, M., Leibel, R. L., & Ferrante Jr, A. W. (2003). Obesity is associated with macrophage accumulation in adipose tissue. Journal of clinical investigation, 112(12), 1796.
Wentworth, J. M., Naselli, G., Brown, W. A., Doyle, L., Phipson, B., Smyth, G. K., Wabitsch, M., O'Brien, P. E. & Harrison, L. C. (2010). Pro-inflammatory CD11c+ CD206+ adipose tissue macrophages are associated with insulin resistance in human obesity. Diabetes, 59(7), 1648-1656.
WHO(10.2017).Obesity and overweight. Retrieved from http://www.who.int/mediacentre/factsheets/fs311/en/ [Accessed 2017.12.20]
WHO.BMI classification.Retrieved from http://apps.who.int/bmi/index.jsp?introPage=intro_3.html [Accessed 2018.01.06]
WHO.Breast cancer: prevention and control.Retrieved from http://www.who.int/cancer/detection/breastcancer/en/index2.html [Accessed 2018.01.02]
Wong, R. S. (2011). Apoptosis in cancer: from pathogenesis to treatment. Journal of Experimental & Clinical Cancer Research, 30(1), 87.
Wu, A. H. (2013). Soy isoflavones and breast cancer. American Society of Clinical Oncology.
Xie, Q., Bai, Q., Zou, L. Y., Zhang, Q. Y., Zhou, Y., Chang, H., Yi, L., Zhu, J. D. & Mi, M. T. (2014). Genistein inhibits DNA methylation and increases expression of tumor suppressor genes in human breast cancer cells. Genes, Chromosomes and Cancer, 53(5), 422-431.
Yamamoto, S., Sobue, T., Kobayashi, M., Sasaki, S., & Tsugane, S. (2003). Soy, isoflavones, and breast cancer risk in Japan. Journal of the national cancer institute, 95(12), 906-913.
Yamauchi, T., Kamon, J., Waki, H., Terauchi, Y., Kubota, N., Hara, K., Mori, Y., Ide, T., Murakami, K., Tsuboyama-Kasaoka, N., Ezaki, O., Akanuma, Y., Gavrilova, O., Vinson, C., Reitman, M. L., Kagechika, H., Shudo, K., Yoda, M., Nakano, Y., Tobe, K., Nagai, R., Kimura, S., Tomita, M., Froguel, P. & Kadowaki, T.. (2001). The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nature medicine, 7(8), 941-946.
Ye, J. (2009). Emerging role of adipose tissue hypoxia in obesity and insulin resistance. International journal of obesity, 33(1), 54.
Ye, J., Gao, Z., Yin, J., & He, Q. (2007). Hypoxia is a potential risk factor for chronic inflammation and adiponectin reduction in adipose tissue of ob/ob and dietary obese mice. American Journal of Physiology-Endocrinology and Metabolism, 293(4), E1118-E1128.
Yu, H., Kortylewski, M., & Pardoll, D. (2007). Tumour immunology: Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment. Nature Reviews Immunology, 7(1), 41.
Zerdes, I., Tsesmetzis, N., Lovrot, J., Rolny, C., Bergh, J. C., Rassidakis, G., & Foukakis, T. (2017). Regulation of PD-L1 in breast cancer.
Zhao, C., Lam, E. W., Sunters, A., Enmark, E., De Bella, M. T., Coombes, R. C., Gustafsson, J. A. & Dahlman-Wright, K. (2003). Expression of estrogen receptor β isoforms in normal breast epithelial cells and breast cancer: regulation by methylation. Oncogene, 22(48), 7600-7606.
Zhao, J., & Lawless, M. W. (2013). Stop feeding cancer: pro-inflammatory role of visceral adiposity in liver cancer. Cytokine, 64(3), 626-637.
Zhao, Y., Agarwal, V. R., Mendelson, C. R., & Simpson, E. R. (1996). Estrogen biosynthesis proximal to a breast tumor is stimulated by PGE2 via cyclic AMP, leading to activation of promoter II of the CYP19 (aromatase) gene. Endocrinology, 137(12), 5739-5742.
Zhao, Y., Tan, Y. S., Aupperlee, M. D., Langohr, I. M., Kirk, E. L., Troester, M. A., Schwartz, R. C. & Haslam, S. Z. (2013). Pubertal high fat diet: effects on mammary cancer development. Breast cancer research, 15(5), R100.
Zhong, H., De Marzo, A. M., Laughner, E., Lim, M., Hilton, D. A., Zagzag, D., Buechler, P., Isaacs, W. B., Semenza, G. L. & Simons, J. W. (1999). Overexpression of hypoxia-inducible factor 1α in common human cancers and their metastases. Cancer research, 59(22), 5830-5835.
Zhou, J. R., Mukherjee, P., Gugger, E. T., Tanaka, T., Blackburn, G. L., & Clinton, S. K. (1998). Inhibition of murine bladder tumorigenesis by soy isoflavones via alterations in the cell cycle, apoptosis, and angiogenesis. Cancer Research, 58(22), 5231-5238.
Zhu, Y., Li, H., & Wang, X. (2017). Lunasin abrogates monocytes to endothelial cells. Molecular immunology, 92, 146-150.