研究生: |
張佳心 Chang, Chia-Hsin |
---|---|
論文名稱: |
Lunasin對MCF-7與MDA-MB-231人類乳癌細胞生長機制之探討 The effects of lunasin on the mechanism of cell growth in 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: |
營養科學碩士學位學程 Graduate Program of Nutrition Science |
論文出版年: | 2020 |
畢業學年度: | 108 |
語文別: | 中文 |
論文頁數: | 102 |
中文關鍵詞: | Lunasin 、乳癌 、雌激素 、芳香酶 、發炎 |
英文關鍵詞: | Lunasin, Breast cancer, Estrogen, Aromarase, Inflammation |
DOI URL: | http://doi.org/10.6345/NTNU202001486 |
論文種類: | 學術論文 |
相關次數: | 點閱:177 下載:0 |
分享至: |
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報 |
癌症為全球死因之首,其中乳癌為女性最常見的癌症種類。流行病學研究發現肥胖為乳癌的危險因子之一,會使身體產生慢性發炎的環境,肥胖的促炎因子也會增加體內芳香酶活性及發炎基因表現量,促使雌激素濃度上升,加速乳癌惡化,雌激素更是停經後婦女誘導乳癌惡化的危險因子之一。Lunasin是一種分子量為5.5 kDa的種子胜肽,由43個胺基酸所組成,研究證實lunasin具有抗氧化、抗發炎、抗癌及降膽固醇等功效,而lunasin對於乳癌細胞的發炎基因表現、細胞激素等調控機制尚未明確,因此本研究欲探討,lunasin是否能藉由調節發炎因子、雌激素受器與芳香酶表現,進而抑制乳癌細胞生長。為了解lunasin對雌激素依賴性MCF-7及非雌激素依賴性MDA-MB-231乳癌細胞影響,以及在雌二醇 (Estradiol, E2)模式下lunasin是否能有效抑制乳癌細胞之生長,進而測試lunasin處理對細胞存活率、發炎基因及細胞激素分泌調控、芳香酶濃度等影響,及E2模式下細胞存活率、細胞活性、細胞週期及細胞凋亡的影響。第一部分為探討lunasin介入對乳癌細胞之影響,結果顯示 l unasin處理顯著抑制兩株乳癌細胞的存活率,而對MCF-10A正常細胞則無細胞毒性,並能降低所有細胞的芳香酶活性及基因表現、抑制ERα基因。在MDA-MB-231細胞方面,lunasin可以降低VEGF濃度和細胞活性,並可增加ERβ及IL-6基因表現及增加MDA-MB-231細胞其細胞凋亡等等 。第二部分為探討雌激素模式下lunasin介入對乳癌細胞之影響,結果顯示E2能顯著增加MCF-7細胞之細胞存活率,而lunasin在E2模式下依舊保有抑制兩株乳癌細胞其細胞存活率之效果,且能降低MCF-7細胞其細胞活性。綜觀上述,lunasin可以藉由降低細胞存活率、促炎基因表現、調控發炎性細胞激素濃度、降低芳香酶活性及增加細胞凋亡等,抑制乳癌腫瘤細胞的生長,因此富含lunasin的飲食可能有助於對乳癌的預防及患者的輔助治療。
Cancer is the leading cause of death worldwide, and breast cancer is the most common type of cancer in women. Epidemiological studies have found that the women with overweight or obesity have higher risk developed breast cancer. The Pro-inflammatory factors of obesity can also increase aromatase activity and inflammatory gene expression in the body, which induces the increase of estrogen concentration and causes estradiol overproduction and also accelerates the deterioration of breast cancer. Estrogen is one of the risk factors for the worsening of breast cancer in postmenopausal women. Lunasin is a seed peptide which consist of 43 amino acids. Studies have confirmed that lunasin has antioxidant, anti-inflammatory, chemoprevention and anti-cancer. However, the effect of lunasin on inflammatory gene expression, cytokines, estrogen receptor and aromatase expression in breast cancer cells has no clear. The aim of this study is intended to find out the whether lunasin can inhibit the growth of MCF-7 and MDA-MB-231 breast cancer cells by regulation of inflammatory factors, estrogen receptor and aromatase expression, and whether lunasin can effectively inhibit the growth of breast cancer cells in the estradiol(E2)-related microenvironment. The first part is to find out the effect of lunasin intervention on breast cancer cells. The results show that lunasin treatment can significantly inhibit the cell viability of breast cancer cells, and can reduce aromatase activity and gene expression, inhibition of all cells ERα gene, reduce the VEGF concentration and cell activity of MDA-MB-231 cells. Furthermore, lunasin can increase the trend of ERβ and IL-6 gene expression and increase the apoptosis of MDA-MB-231 cells. The second part is to investigate the effect of lunasin treat on breast cancer cells in the E2-related microenvironment. The results show that E2 can significantly increase the cell viability of MCF-7 cells, while lunasin still inhibits the cell viability of breast cancer cells in E2-related microenvironment. In addition, lunasin can reduce the cell vitality MCF-7 cells. In summary, lunasin can inhibit the growth of breast cancer cells by reducing cell viability, pro-inflammatory gene expression, regulating the concentration of inflammatory cytokines, reducing aromatase activity, and increasing breast cancer cells apoptosis. Therefore, the diet rich in lunasin may have contribute to the prevention of breast cancer and be a promising adjuvant therapy to related breast cancer.
American Cancer Society(09.2017). Types of Breast Cancer. Retrieved fromhttps://www.cancer.org/cancer/breast-cancer/understanding-a-breast-cancer-diagnosis/types-of-breast-cancer.html [Accessed 2019.02.10]
Adebayo, I., Arsad, H., & Samian, M. R. (2017) ANTIPROLIFERATIVE EFFECT ON BREAST CANCER (MCF7) OF MORINGA OLEIFERA SEED EXTRACTS. Afr J Tradit Complement Altern Med. 13, 14(2), 282-287.
Akram M, Iqbal M, Daniyal M, Khan AU. Awareness and current knowledge of breast cancer. Biol Res. 2017;50(1):33. Published 2017 Oct 2. doi:10.1186/s40659-017-0140-9
Andò, S., Barone, I., Giordano, C., Bonofiglio, D., & Catalano, S. (2014) The Multifaceted Mechanism of Leptin Signaling within Tumor Microenvironment in Driving Breast Cancer Growth and Progression. Frontiers in Oncology, 4, 340.
Antoniou A, Pharoah PD, Narod S, et al. Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies [published correction appears in Am J Hum Genet. 2003 Sep;73(3):709]. Am J Hum Genet. 2003;72(5):1117-1130. doi:10.1086/375033
Arcidiacono, B., Iiritano, S., Nocera, A., Possidente, K., Nevolo, M. T., Ventura, V., Foti, D., Chiefari, E., & Brunetti, A. (2012) Insulin resistance and cancer risk: an overview of the pathogenetic mechanisms. Experimental Diabetes Research, 2012, 789174.
Aune D, Chan DS, Greenwood DC, et al. Dietary fiber and breast cancer risk: a systematic review and meta-analysis of prospective studies. Ann Oncol. 2012;23(6):1394-1402. doi:10.1093/annonc/mdr589
Balkwill, F., Charles, K. A., & Mantovani, A. (2005) Smoldering and polarized inflammation in the initiation and promotion of malignant disease. Cancer Cell. 7(3), 211-7.
Blüher, M. (2019) Obesity: global epidemiology and pathogenesis. Nat Rev Endocrinol. 15(5), 288-298.
Bochet, L., Lehuédé, C., Dauvillier, S., Wang, Y. Y., Dirat, B., Laurent, V., Dray, C., Guiet, R., Maridonneau-Parini, I., Le Gonidec, S., Couderc, B., Escourrou, G., Valet, P., & Muller, C. (2013) Adipocyte-derived fibroblasts promote tumor progression and contribute to the desmoplastic reaction in breast cancer. Cancer Res. 15, 73(18), 5657-68.
Böhm I, Schild H (2003). "Apoptosis: the complex scenario for a silent cell death". Molecular Imaging and Biology. 5 (1): 2–14.
Boon, W. C., Chow, J. D., & Simpson, E. R. (2010) The multiple roles of estrogens and the enzyme aromatase. Progress in Brain Research, 181, 209-32.
Bray, G. A., Kim, K. K., & Wilding, J. P. H.,World Obesity Federation. (2017) Obesity: a chronic relapsing progressive disease process. A position statement of the World Obesity Federation. Obes Rev. 18(7), 715-723.
Bray, F., Ferlay, J., Soerjomataram I., Siegel, R. L., & Torre, L. A. (2018) Jemal A.Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 68(6), 394-424.
Brodie, A. M., Lu, Q., Long, B. J., Fulton, A., Chen, T., Macpherson, N., DeJong, P. C., Blankenstein, M. A., Nortier, J. W., Slee, P. H., Van, D. V. J., Van, G. J. M., Elbers, J. R., Schipper, M. E., Blijham, G. H., & Thijssen, J. H. (2001) Aromatase and COX-2 expression in human breast cancers. The Journal of Steroid Biochemistry and Molecular Biology, 79(1-5), 41-7.
Brooks, J. D., & Thompson, L.U. (2005) Mammalian lignans and genistein decrease the activities of aromatase and 17beta-hydroxysteroid dehydrogenase in MCF-7 cells. J Steroid Biochem Mol Biol. 94(5), 461-7.
Brown, K. A., McInnes, K. J., Hunger, N. I., Oakhill, J. S., Steinberg, G. R., Simpson, E. R. (2009) Subcellular localization of cyclic AMP-responsive element binding protein-regulated transcription coactivator 2 provides a link between obesity and breast cancer in postmenopausal women. Cancer Research, 69(13), 5392-9.
Brown, K.A., Simpson, E.R. (2012) Obesity and breast cancer: mechanisms and therapeutic implications. Frontiers in Bioscience, 4, 2515-24.
Brown, K. A., Iyengar, N. M., Zhou, X. K., Gucalp, A., Subbaramaiah, K., Wang, H., Giri, D. D., Morrow, M., Falcone, D. J., Wendel, N. K., Winston, L. A., Pollak, M., Dierickx, A., Hudis, C. A., & Dannenberg, A. J. (2017) Menopause is a determinant of breast aromatase expression and its associations with BMI, inflammation, and systemic markers. J. Clin. Endocrinol. Metab. 102, 1692-1701
Bulun, S. E., Sharda, G., Rink, J., Sharma, S., & Simpson, E. R. (1996) Distribution of aromatase P450 transcripts and adipose fibroblasts in the human breast. J Clin Endocrinol Metab. 81(3), 1273-7.
Bulun, S. E., Lin, Z., Imir, G., Amin, S., Demura, M., Yilmaz, B., Martin, R., Utsunomiya, H., Thung, S., Gurates, B., Tamura, M., Langoi, & D., Deb, S. (2005) Regulation of aromatase expression in estrogen-responsive breast and uterine disease: from bench to treatment. Pharmacological Reviews, 57(3), 359-83.
Bulun, S. E., Chen, D., Moy, I., Brooks, D. C., & Zhao, H. (2012) Aromatase, breast cancer and obesity: a complex interaction. Trends Endocrinology Metabolism, 23(2), 83-9.
Buzdar, A., & Howell, A. (2001) Advances in aromatase inhibition: clinical efficacy and tolerability in the treatment of breast cancer. Clinical Cancer Research, 7(9), 2620-35.
Calle, E. E., & Kaaks, R. (2004) Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nature Reviews Cancer, 4(8), 579-91.
Cam A, de Mejia EG. RGD-peptide lunasin inhibits Akt-mediated NF-κB activation in human macrophages through interaction with the αVβ3 integrin. Mol Nutr Food Res. 2012;56(10):1569-1581. doi:10.1002/mnfr.201200301
Cecchini, R. S., Costantino, J. P., Cauley, J. A., Cronin, W. M., Wickerham, D. L., Land, S. R., Weissfeld, J. L., & Wolmark, N. (2012) Body mass index and the risk for developing invasive breast cancer among high-risk women in NSABP P-1 and STAR breast cancer prevention trials. Cancer Prev Res (Phila). 5(4), 583-92.
Chang, Q., Bournazou, E., Sansone, P., Berishaj, M., Gao, S. P., Daly, L., Wels, J., Theilen, T., Granitto, S., Zhang, X., Cotari, J., Alpaugh, M. L., de Stanchina, E., Manova, K., Li, M., Bonafe, M., Ceccarelli, C., Taffurelli, M., Santini, D., Altan-Bonnet, G., Kaplan, R., Norton, L., Nishimoto, N., Huszar, D., Lyden, D., & Bromberg, J. (2013) The IL-6/JAK/Stat3 feed-forward loop drives tumorigenesis and metastasis. Neoplasia. 15(7), 848-62.
Chang HC, Lewis D, Tung CY, et al. Soypeptide lunasin in cytokine immunotherapy for lymphoma. Cancer Immunol Immunother. 2014;63(3):283-295.
Chi, F., Wu, R., Zeng, Y. C., Xing, R., Liu, Y., & Xu, Z. G. (2013) Post-diagnosis soy food intake and breast cancer survival: a meta-analysis of cohort studies. Asian Pac J Cancer Prev. 14(4), 2407-12.
Choi, J., Cha, Y. J., & Koo, J. S. (2018) Adipocyte biology in breast cancer: From silent bystander to active facilitator. Progress in Lipid Research, 69, 11-20.
Conde, J., Scotece, M., Gómez, R., López, V., Gómez-Reino, J. J., Lago, F., & Gualillo, O. (2011) Adipokines: biofactors from white adipose tissue. A complex hub among inflammation, metabolism, and immunity. Biofactors. 37(6), 413-20.
Considine, R. V., Sinha, M. K., Heiman, M. L., Kriauciunas, A., Stephens, T. W., Nyce, M. R., Ohannesian, J. P., Marco, C. C., McKee, L. J., & Bauer, T. L. (1996) Serum immunoreactive-leptin concentrations in normal-weight and obese humans. The New England Journal of Medicine, 334(5), 292-5.
Couse, J. F., & Korach, K. S. (1999) Estrogen receptor null mice: what have we learned and where will they lead us? Endocr Rev. 20(3), 358-417.
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 Funct. 6(8), 2626-35.
De, U., Son, J. Y., Jeon, Y., Ha, S. Y., Park, Y. J., Yoon, S., Ha, K. T., Choi, W. S., Lee, B. M., Kim, I. S., Kwak, J. H., & Kim, H. S. (2019) Plumbagin from a tropical pitcher plant (Nepenthes alata Blanco) induces apoptotic cell death via a p53-dependent pathway in MCF-7 human breast cancer cells. Food Chem Toxicol. 123, 492-500.
Dieudonne, M. N., Bussiere, M., Dos Santos, E., Leneveu, M. C., Giudicelli, Y., & Pecquery, R. (2006) Adiponectin mediates antiproliferative and apoptotic responses in human MCF7 breast cancer cells. Biochemical and Biophysical Research Communications, 345(1), 271-9.
Dia, V. P., Torres, S., De Lumen, B. O., Erdman, J. W. Jr., De Mejia, E. G. (2009) Presence of lunasin in plasma of men after soy protein consumption. J Agric Food Chem. 25, 57(4), 1260-6.
Dia VP, Mejia EG. Lunasin promotes apoptosis in human colon cancer cells by mitochondrial pathway activation and induction of nuclear clusterin expression. Cancer Lett. 2010;295(1):44-53. doi:10.1016/j.canlet.2010.02.010
Dirat, B., Bochet, L., Dabek, M., Daviaud, D., Dauvillier, S., Majed, B., Wang, Y. Y., Meulle, A., Salles, B., Le Gonidec, S., Garrido, I., Escourrou, G., Valet, P., & Muller, C. (2011) Cancer-associated adipocytes exhibit an activated phenotype and contribute to breast cancer invasion. Cancer Res. 1, 71(7), 2455-65.
Dong JY, Qin LQ. Soy isoflavones consumption and risk of breast cancer incidence or recurrence: a meta-analysis of prospective studies. Breast Cancer Res Treat. 2011;125(2):315-323. doi:10.1007/s10549-010-1270-8
Dubois, V., Jardé, T., Delort, L., Billard, H., Bernard-Gallon, D., Berger, E., Geloen, A.,Vasson, M. P., & Caldefie-Chezet, F. (2014) Leptin induces a proliferative response in breast cancer cells but not in normal breast cells. Nutrition and Cancer, 66(4), 645-55.
Dzirkale Z, Nakurte I, Jekabsons K, Muceniece R, Klusa V. Intra-Nasally Administered Oligopeptide Lunasin Acts as a Possible Anti-Psychotic Agent in Mice Models. Medicina (Kaunas). 2019;55(7):393. Published 2019 Jul 21. doi:10.3390/medicina55070393
Engin, A. (2017) The Definition and Prevalence of Obesity and Metabolic Syndrome. Adv Exp Med Biol. 960, 1-17.
Fernández-Tomé, S., Sanchón, J., Recio, I. & Hernández-Ledesma, B. (2017) Transepithelial transport of lunasin and derived peptides: inhibitory effects on the gastrointestinal cancer cells viability. J Food Comp Anal. 68, 101-110.
Fernández-Tomé S, Hernández-Ledesma B. Current state of art after twenty years of the discovery of bioactive peptide lunasin. Food Res Int. 2019;116:71-78. doi:10.1016/j.foodres.2018.12.029
Foster DA, Yellen P, Xu L, Saqcena M. Regulation of G1 Cell Cycle Progression: Distinguishing the Restriction Point from a Nutrient-Sensing Cell Growth Checkpoint(s). Genes Cancer. 2010;1(11):1124-1131. doi:10.1177/1947601910392989
Friebel, T. M., Domchek, S. M., & Rebbeck, T. R. (2014) Modifiers of cancer risk in BRCA1 and BRCA2 mutation carriers: systematic review and meta-analysis. J Natl Cancer Inst. 106(6), dju091.
Gallo, D., Giacomelli, S., Cantelmo, F., Zannoni, G. F., Ferrandina, G., Fruscella, E., Riva, A., Morazzoni, P., Bombardelli, E., Mancuso, S., & Scambia, G (2001) . Chemoprevention of DMBA-induced mammary cancer in rats by dietary soy. Breast Cancer Res Treat. 69(2), 153-64.
Galvez AF, de Lumen BO. A soybean cDNA encoding a chromatin-binding peptide inhibits mitosis of mammalian cells. Nat Biotechnol. 1999;17(5):495-500. doi:10.1038/8676
Galvez, A.F., Chen, N., Macasieb, J., & de Lumen, B. O. (2001) Chemopreventive property of a soybean peptide (lunasin) that binds to deacetylated histones and inhibits acetylation. Cancer Res. 15, 61(20), 7473-8.
Gascón, F., Valle, M., Martos, R., Ruz, F. J., Ríos, R., Montilla, P., & Cañete, R. (2000) Sex hormone-binding globulin as a marker for hyperinsulinemia and/or insulin resistance in obese children. European Journal of Endocrinology, 143(1), 85-9.
Gao, S., Sun, Y., Liu, X., Zhang, D., & Yang, X. (2017) EpCAM and COX‑2 expression are positively correlated in human breast cancer. Mol Med Rep. 15(6), 3755-3760.
Gérard, C., & Brown, K. A. (2018) Obesity and breast cancer - Role of estrogens and the molecular underpinnings of aromatase regulation in breast adipose tissue. Molecular and Cellular Endocrinology, 466, 15-30.
Garcia-Tuñón, I., Ricote, M., Ruiz, A., Fraile, B., Paniagua, R., & Royuela, M. (2005) IL-6, its receptors and its relationship with bcl-2 and bax proteins in infiltrating and in situ human breast carcinoma. Histopathology. 47(1), 82-9.
García-Nebot MJ, Recio I, Hernández-Ledesma B. Antioxidant activity and protective effects of peptide lunasin against oxidative stress in intestinal Caco-2 cells. Food Chem Toxicol. 2014;65:155-161. doi:10.1016/j.fct.2013.12.021
Geyer, F. C., Rodrigues, D. N., Weigelt, B., & Reis-Filho, J. S. (2012) Molecular classification of estrogen receptor-positive/luminal breast cancers. Advances in Anatomic Pathology, 19(1), 39-53.
Ghosh, A.K. (2003) Regulation by prostaglandin E2 and histamine of angiogenesis ininflammatory granulation tissue. Yakugaku Zasshi, 123 (5), 295e303.
Global Burden of Disease Cancer Collaboration, et al. (2017) Global, regional,and national cancer incidence, mortality, years of life lost, years lived with disability, and disability adjusted life-years for 32 Cancer Groups 1990 to 2015: a systematic analysis for the Global Burden of Disease Study. JAMA Oncol, 3(4), 524–48.
Girgert, R., Emons, G., & Gründker, C. (2019) Estrogen Signaling in ERα-Negative Breast Cancer: ERβ and GPER. Front Endocrinol (Lausanne). 9, 9, 781.
Gonzalez de, M. E., Vásconez, M., de Lumen, B. O., & Nelson, R. (2004) Lunasin concentration in different soybean genotypes, commercial soy protein, and isoflavone products. J Agric Food Chem. 22, 52(19), 5882-7.
Gruvberger-Saal, S. K., Bendahl, P. O., Saal, L. H., Laakso, M., Hegardt, C., Edén, P., Peterson, C., Malmström, P., Isola, J., Borg, A., & Fernö, M. (2007) Estrogen receptor beta expression is associated with tamoxifen response in ERalpha-negative breast carcinoma. Clin Cancer Res. 1, 13(7), 1987-94.
Gu L, Gong Y, Zhao C, et al. Lunasin Improves the LDL-C Lowering Efficacy of Simvastatin via Inhibiting PCSK9 Expression in Hepatocytes and ApoE-/- Mice. Molecules. 2019;24(22):4140. Published 2019 Nov 15. doi:10.3390/molecules24224140
Håkonsen, L. B., Thulstrup, A. M., Aggerholm, A. S., Olsen, J., Bonde, J. P., Andersen, C. Y., Bungum, M., Ernst, E. H., Hansen, M. L., Ernst, E. H., Ramlau-Hansen, C. H. (2011) Does weight loss improve semen quality and reproductive hormones? Results from a cohort of severely obese men. Reprod Health. 17, 8, 24.
Haldosén, L. A., Zhao, C., & Dahlman-Wright, K. (2014) Estrogen receptor beta in breast cancer. Mol Cell Endocrinol. 25, 382(1), 665-672.
Harris, R. E., Casto, B. C., & Harris, Z. M. (2014) Cyclooxygenase-2 and the inflammogenesis of breast cancer. World J Clin Oncol. 10, 5(4), 677-92.
Hartman, J., Lindberg, K., Morani, A., Inzunza, J., Ström, A., & Gustafsson, J. A. (2006) Estrogen receptor beta inhibits angiogenesis and growth of T47D breast cancer xenografts. Cancer Res. 1, 66(23), 11207-13.
Harvie M, Howell A, Evans DG. Can diet and lifestyle prevent breast cancer: what is the evidence?. Am Soc Clin Oncol Educ Book. 2015;e66-e73. doi:10.14694/EdBook_AM.2015.35.e66
Heinrich, P. C., Castell, J. V., & Andus, T. (1990) Interleukin-6 and the acute phase response. Biochem J. 265, 621–636.
He, J. Y., Wei, X. H., Li, S.J., Liu, Y., Hu, H. L., Li, Z. Z., Kuang, X. H., Wang, L., Shi, X., Yuan, S. T., & Sun, L. (2018) Adipocyte-derived IL-6 and leptin promote breast Cancer metastasis via upregulation of Lysyl Hydroxylase-2 expression. Cell Commun Signal. 18, 16(1), 100.
Heo, T. H., Wahler, J., & Suh, N., (2016) Potential therapeutic implications of IL-6/IL-6R/gp130-targeting agents in breast cancer. Oncotarget. 29, 7(13), 15460-73.
Hernández-Ledesma B, Hsieh CC, de Lumen BO. Antioxidant and anti-inflammatory properties of cancer preventive peptide lunasin in RAW 264.7 macrophages. Biochem Biophys Res Commun. 2009;390(3):803-808. doi:10.1016/j.bbrc.2009.10.053
Hernández-Ledesma, B., Hsieh, C. C., & de Lumen, B. O. (2011) Relationship between lunasin's sequence and its inhibitory activity of histones H3 and H4 acetylation. Mol Nutr Food Res. 55(7), 989-98.
Hoy, A. J., Balaban, S., & Saunders, D. N. (2017) Adipocyte-Tumor Cell Metabolic Crosstalk in Breast Cancer. Trends Mol Med. 23(5), 381-392.
Honma, N., Horii, R., Iwase, T., Saji, S., Younes, M., Takubo, K., Matsuura, M., Ito, Y., Akiyama, F., & Sakamoto, G. (2008) Clinical importance of estrogen receptor-beta evaluation in breast cancer patients treated with adjuvant tamoxifen therapy. J Clin Oncol. 1, 26(22), 3727-34.
Hsieh CC, Hernández-Ledesma B, de Lumen BO. Lunasin, a novel seed peptide, sensitizes human breast cancer MDA-MB-231 cells to aspirin-arrested cell cycle and induced apoptosis. Chem Biol Interact. 2010;186(2):127-134. doi:10.1016/j.cbi.2010.04.027
Hsieh, C. C., Hernández-Ledesma, B., & de Lumen, B. O. (2010) Lunasin, a novel seed peptide, sensitizes human breast cancer MDA-MB-231 cells to aspirin-arrested cell cycle and induced apoptosis. Chem Biol Interact. 30, 186(2):127-34.
Hsieh CC,Shih-Han Peng, Chia-Hsin Chang. (2020) The effects of lunasin on the mechanism of cell growth in MCF-7 and MDA-MB-231 human breast cancer cells. Manuscript.
Hsieh, C. Y., Santell, R. C., Haslam, S. Z., & Helferich, W. G. (1998) Estrogenic effects of genistein on the growth of estrogen receptor-positive human breast cancer (MCF-7) cells in vitro and in vivo. Cancer Res. 1, 58(17), 3833-8.
Hsieh CC, Wang CH, Huang YS. Lunasin Attenuates Obesity-Associated Metastasis of 4T1 Breast Cancer Cell through Anti-Inflammatory Property. Int J Mol Sci. 2016;17(12):2109. Published 2016 Dec 15. doi:10.3390/ijms17122109
Hsieh CC, Chou MJ, Wang CH. Lunasin attenuates obesity-related inflammation in RAW264.7 cells and 3T3-L1 adipocytes by inhibiting inflammatory cytokine production. PLoS One. 2017;12(2):e0171969. Published 2017 Feb 9. doi:10.1371/journal.pone.0171969
Hu S, Xu Y, Meng L, Huang L, Sun H. Curcumin inhibits proliferation and promotes apoptosis of breast cancer cells. Exp Ther Med. 2018;16(2):1266-1272.
Huang, J. H., Zhang, J., & Zager, E. L. (2005) Diagnosis and treatment options for nerve sheath tumors. Expert Rev Neurother. 5(4), 515-23.
Huang L, Li A, Liao G, et al. Curcumol triggers apoptosis of p53 mutant triple-negative human breast cancer MDA-MB 231 cells via activation of p73 and PUMA. Oncol Lett. 2017;14(1):1080-1088. doi:10.3892/ol.2017.6273
Hulka, B. S., & Moorman, P. G. (2001) Breast cancer: hormones and other risk factors. Maturitas, 61(1-2), 203-13.
Inaba J, McConnell EJ, Davis KR. Lunasin sensitivity in non-small cell lung cancer cells is linked to suppression of integrin signaling and changes in histone acetylation. Int J Mol Sci. 2014;15(12):23705-23724. Published 2014 Dec 18. doi:10.3390/ijms151223705
Israel, B. B., Tilghman, S. L., Parker-Lemieux, K., & Payton-Stewart, F. (2018) Phytochemicals: Current strategies for treating breast cancer. Oncol Lett. 15(5), 7471-7478.
Iyengar, N. M., Morris, P. G., Zhou, X. K., Gucalp, A., Giri, D., Harbus, M. D., Falcone, D. J., Krasne, M. D., Vahdat, L. T., Subbaramaiah, K., Morrow, M., Hudis, C. A., & Dannenberg, A. J. (2015) Menopause is a determinant of breast adipose infl ammation. Cancer Prev. Res. (Phila.) 8, 349-358
Iyengar, N. M., Gucalp, A., Dannenberg, A. J., & Hudis, C. A. (2016) Obesity and Cancer Mechanisms: Tumor Microenvironment and Inflammation. J Clin Oncol. 34(35), 4270-4276.
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., & Dannenberg, A. J. (2017) Metabolic Obesity, Adipose Inflammation and Elevated Breast Aromatase in Women with Normal Body Mass Index. Cancer Prevention Research, 10(4), 235-243.
Izaola, O., de Luis, D., Sajoux, I., Domingo, J. C., & Vidal, M. (2015) Inflammation and obesity (lipoinflammation) Nutr Hosp. 31(6), 2352-8.
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 J. Surg. Oncol. 5 (1), 59e65.
JavanMoghadam S, Weihua Z, Hunt KK, Keyomarsi K. Estrogen receptor alpha is cell cycle-regulated and regulates the cell cycle in a ligand-dependent fashion. Cell Cycle. 2016;15(12):1579-1590. doi:10.1080/15384101.2016.1166327
Jemal, A., Bray, F., Center, M. M., Ferlay, J., Ward, E., & Forman, D. (2011) Global cancer statistics. CA: A Cancer Journal for Clinicians, 61(2), 69-90.
Jeong HJ, Lam Y, de Lumen BO. (2002) Barley lunasin suppresses ras-induced colony formation and inhibits core histone acetylation in mammalian cells. J Agric Food Chem. 50(21):5903-5908. doi:10.1021/jf0256945
Jeong HJ, Park JH, Lam Y, de Lumen BO. (2003) Characterization of lunasin isolated from soybean. J Agric Food Chem.;51(27):7901-7906. doi:10.1021/jf034460y
Jeong HJ, Jeong JB, Kim DS, et al. The cancer preventive peptide lunasin from wheat inhibits core histone acetylation. Cancer Lett. 2007;255(1):42-48. doi:10.1016/j.canlet.2007.03.022
Jeong, H. J., Lee, J. R., Jeong, J. B., Park, J. H., Cheong, Y. K., & de Lumen, B. O. (2009) The cancer preventive seed peptide lunasin from rye is bioavailable and bioactive. Nutr Cancer. 61(5), 680-6.
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 Res Int. 2015, 346839.
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. Oncol Rep. 36(1), 253-62.
Jin, S., Zhang, Q. Y., Kang, X. M., Wang, J. X., & Zhao, W. H. (2010) Daidzein induces MCF-7 breast cancer cell apoptosis via the mitochondrial pathway. Ann Oncol. 21(2), 263-8.
Johnson, D. E., O'Keefe, R. A., & Grandis, J. R. (2018) Targeting the IL-6/JAK/STAT3 signalling axis in cancer. Nat Rev Clin Oncol. 15(4), 234-248.
Jones, R. A., Campbell, C. I., Gunther, E. J., Chodosh, L. A., Petrik, J. J., Khokha, R., & Moorehead, R. A. (2007) Transgenic overexpression of IGF-IR disrupts mammary ductal morphogenesis and induces tumor formation. Oncogene, 26(11), 1636-44.
Ju, Y. H., Fultz, J., Allred, K. F., Doerge, D. R., & Helferich, W. G. (2006) Effects of dietary daidzein and its metabolite, equol, at physiological concentrations on the growth of estrogen-dependent human breast cancer (MCF-7) tumors implanted in ovariectomized athymic mice. Carcinogenesis. 27(4), 856-63.
Keaver, L., L. Webber, A. Dee, F. Shiely, T. Marsh, K. Balanda, I.J. Perry, & I. Perry. (2013) Application of the UK foresight obesity model in Ireland: The health and economic consequences of projected obesity trends in Ireland. PLoS One 8: e79827.
Kelsey JL, Bernstein L. Epidemiology and prevention of breast cancer. Annu Rev Public Health. 1996;17:47-67. doi:10.1146/annurev.pu.17.050196.000403
Key TJ, Verkasalo PK, Banks E. Epidemiology of breast cancer. Lancet Oncol. 2001;2(3):133-140. doi:10.1016/S1470-2045(00)00254-0
Kim SE, Kim HH, Kim JY, Kang YI, Woo HJ, Lee HJ. Anticancer activity of hydrophobic peptides from soy proteins. Biofactors. 2000;12(1-4):151-155. doi:10.1002/biof.5520120124
Klotz, D. M., Hewitt, S. C., Ciana, P., Raviscioni, M., Lindzey, J. K., Foley, J., Maggi, A., DiAugustine, R. P., & Korach, K. S. (2002) Requirement of estrogen receptor-alpha in insulin-like growth factor-1 (IGF-1)-induced uterine responses and in vivo evidence for IGF-1/estrogen receptor cross-talk. The Journal of Biological Chemistry, 277(10), 8531-7.
Krege, J. H., Hodgin, J. B., Couse, J. F., Enmark, E., Warner, M., Mahler, J. F., Sar, M., Korach, K. S., Gustafsson, J. A., & Smithies, O. (1998) Generation and reproductive phenotypes of mice lacking estrogen receptor beta. Proc Natl Acad Sci U S A. 22, 95(26), 15677-82.
Kubatka, P., Uramova, S., Kello, M., Kajo, K., Samec, M., Jasek, K., Vybohova, D., Liskova, A., Mojzis, J., Adamkov, M., Zubor, P., Smejkal, K., Svajdlenka, E., Solar, P., Samuel, S. M., Zulli, A., Kassayova, M., Lasabova, Z., Kwon, T. K., Pec, M., Danko, J., & Büsselberg, D. (2019) Anticancer Activities of Thymus vulgaris L. in Experimental Breast Carcinoma in Vivo and in Vitro. Int J Mol Sci. 9, 20(7).
Kusmardi K, Nessa N, Estuningtyas A, Tedjo A. The effect of lunasin from Indonesian soybean extract on histopatologic examination and cox-2 expression in dextran sodium sulfate-induced mice colon. Int J Physiol Pathophysiol Pharmacol. 2018;10(6):154-162.
Kyle, T. K., Dhurandhar, E. J., & Allison, D. B. (2016) Regarding obesity as a disease. Endocrinol Metab Clin N Am, 45, 511-520
Lam Y, Galvez A, de Lumen BO. Lunasin suppresses E1A-mediated transformation of mammalian cells but does not inhibit growth of immortalized and established cancer cell lines. Nutr Cancer. 2003;47(1):88-94. doi:10.1207/s15327914nc4701_11
Lam, J. B., Chow, K. H., Xu, A., Lam, K. S., Liu, J., Wong, N. S., Moon, R. T., Shepherd, P. R., Cooper, G. J., & Wang, Y. (2009) Adiponectin haploinsufficiency promotes mammary tumor development in MMTV-PyVT mice by modulation of phosphatase and tensin homolog activities. PLOS ONE, 4(3), e4968.
Lammi C., Zanoni C., Arnoldi A. IAVPGEVA, IAVPTGVA, and LPYP, three peptides from soy glycinin, modulate cholesterol metabolism in HepG2 cells through the activation of the LDLR-SREBP2 pathway. J. Funct. Foods. 2015;14:469–478. doi: 10.1016/j.jff.2015.02.021.
Lecke, S. B., Morsch, D. M., & Spritzer, P. M. (2011) Leptin and adiponectin in the female life course. Brazilian Journal of Medical and Biological Research, 44(5), 381-7.
Le Romancer, M., Poulard, C., Cohen, P., Sentis, S., Renoir, J. M., & Corbo, L. (2011) Cracking the estrogen receptor's posttranslational code in breast tumors. Endocrine Reviews, 32(5), 597-622.
Li, Y., Li, S., Meng, X., Gan, R. Y., Zhang, J. J., & Li, H. B. (2017) Dietary Natural Products for Prevention and Treatment of Breast Cancer. Nutrients. 8, 9(7).
Liang, J., & Shang, Y. (2013) Estrogen and cancer. Annual Review of Physiology, 75,225-40.
Lin YY, Chen JS, Wu XB, et al. Combined effects of 17β-estradiol and exercise training on cardiac apoptosis in ovariectomized rats. PLoS One. 2018;13(12):e0208633. Published 2018 Dec 20. doi:10.1371/journal.pone.0208633
Lisa M. A., & Charlotte K. (2015) Working stiff: How obesity boosts cancer risk. Science Translational Medicine, 7(301), 301fs34.
Liyanage R, Han KH, Watanabe S, et al. Potato and soy peptide diets modulate lipid metabolism in rats. Biosci Biotechnol Biochem. 2008;72(4):943-950. doi:10.1271/bbb.70593
Lule VK, Garg S, Pophaly SD, Hitesh, Tomar SK. "Potential health benefits of lunasin: a multifaceted soy-derived bioactive peptide". J Food Sci. 2015;80(3):R485-R494. doi:10.1111/1750-3841.12786
Madhu Krishna, B., Chaudhary, S., Mishra, D. R., Naik, S. K., Suklabaidya, S., Adhya, A. K., & Mishra, S. K. (2018) Estrogen receptor α dependent regulation of estrogen related receptor β and its role in cell cycle in breast cancer. BMC Cancer. 30, 18(1), 607.
Malara NM, Leotta A, Sidoti A, et al. Ageing, hormonal behaviour and cyclin D1 in ductal breast carcinomas. Breast. 2006;15(1):81-89. doi:10.1016/j.breast.2004.12.008
Marotti, J. D., Collins, L. C., Hu, R., & Tamimi, R. M. (2010) Estrogen receptor-beta expression in invasive breast cancer in relation to molecular phenotype: results from the Nurses' Health Study. Mod Pathol. 23(2), 197-204.
McConnell EJ, Devapatla B, Yaddanapudi K, Davis KR. The soybean-derived peptide lunasin inhibits non-small cell lung cancer cell proliferation by suppressing phosphorylation of the retinoblastoma protein. Oncotarget. 2015;6(7):4649-4662.
McPherson K, Steel CM, Dixon JM. ABC of breast diseases. Breast cancer-epidemiology, risk factors, and genetics. BMJ. 2000;321(7261):624-628. doi:10.1136/bmj.321.7261.624
Messina, M. (2016) Impact of Soy Foods on the Development of Breast Cancer and the Prognosis of Breast Cancer Patients. Forsch Komplementmed. 23(2), 75-80.
Mitchell RA, Lovegrove A, Shewry PR. (2013) Lunasin in cereal seeds: What is the origin?. J Cereal ;57(3):267-269.
Mizuno R, Kawada K, Sakai Y. Prostaglandin E2/EP Signaling in the Tumor Microenvironment of Colorectal Cancer. Int J Mol Sci. 2019;20(24):6254. Published 2019 Dec 11. doi:10.3390/ijms20246254
Morris, P. G., Hudis, C. A., Giri, D., Morrow, M., Falcone, D. J., Zhou, X. K., Du, B., Brogi, E., Crawford, C. B., Kopelovich, L., Subbaramaiah, K., & Dannenberg, A. J. (2011) Inflammation and increased aromatase expression occur in the breast tissue of obese women with breast cancer. Cancer Prev Res (Phila), 4(7), 1021-9.
Mourouti, N., Kontogianni, M. D., Papavagelis, C., & Panagiotakos, D. B. (2015) Diet and breast cancer: a systematic review. Int J Food Sci Nutr. 66(1), 1-42.
Nagaraju, G. P., Rajitha, B., Aliya, S., Kotipatruni, R. P., Madanraj, A. S., Hammond, A., Park, D., Chigurupati, S., Alam, A., & Pattnaik, S. (2016) The role of adiponectin in obesity-associated female-specific carcinogenesis. Cytokine & Growth Factor Reviews, 31, 1-7.
Nakurte I., Klavins K., Kirhnere I., Namniece J., Adlere L., Matvejevs J., Kronberga A., Kokare A., Strazdina V., Legzdina L., Muceniece R. Discovery of lunasin peptide in triticale (X Triticosecale Wittmack) Journal of Cereal Science. 2012;56:510–514.
NCD Risk Factor Collaboration (NCD-RisC). (2017) Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128·9 million children, adolescents, and adults. Lancet, 16, 390(10113), 2627-2642.
Odani S, Koide T, Ono T. Amino acid sequence of a soybean (Glycine max) seed polypeptide having a poly(L-aspartic acid) structure. J Biol Chem. 1987;262(22):10502-10505.
Pabona JM, Dave B, Su Y, et al. 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 Nutr. 2013;8(1):79-90. doi:10.1007/s12263-012-0307-5
Panno, M. L., Naimo, G. D., Spina, E., Andò, S., & Mauro, L. (2016) Different molecular signaling sustaining adiponectin action in breast cancer. Current Opinion in Pharmacology, 31, 1-7.
Park, J. H., Jeong, H. J., & Lumen, B. O. (2007) In vitro digestibility of the cancer-preventive soy peptides lunasin and BBI. J Agric Food Chem. 26, 55(26),10703-6.
Park K, Choi K, Kim H, et al. Isoflavone-deprived soy peptide suppresses mammary tumorigenesis by inducing apoptosis. Exp Mol Med. 2009;41(6):371-381. doi:10.3858/emm.2009.41.6.042
Paterni, I, Granchi, C., Katzenellenbogen, J. A., & Minutolo, F. (2014) Estrogen receptors alpha (ERα) and beta (ERβ): subtype-selective ligands and clinical potential. Steroids. 90, 13-29.
Patten RD, Pourati I, Aronovitz MJ, et al. 17beta-estradiol reduces cardiomyocyte apoptosis in vivo and in vitro via activation of phospho-inositide-3 kinase/Akt signaling. Circ Res. 2004;95(7):692-699. doi:10.1161/01.RES.0000144126.57786.89
Péqueux, C., Raymond-L, I., Blacher, S., Boudou, F., Adlanmerini, M., Fouque, M. J., Rochaix, P., Noël, A., Foidart, J. M., Krust, A., Chambon, P., Brouchet, L., Arnal, J. F., & Lenfant, F. (2012) Stromal estrogen receptor-α promotes tumor growth by normalizing an increased angiogenesis. Cancer Research, 72(12), 3010-9.
Pettapiece-Phillips, R., Narod, S. A., & Kotsopoulos, J. (2015) The role of body size and physical activity on the risk of breast cancer in BRCA mutation carriers. Cancer Causes Control, 26(3), 333-44.
Philippou, A., Maridaki, M., Pneumaticos, S., & Koutsilieris, M. (2014) The complexity of the IGF1 gene splicing, posttranslational modification and bioactivity. Molecular Medicine, 20, 202-14.
Picon‐Ruiz, M., Morata‐Tarifa, C., Valle‐Goffin, J. J., Friedman, E. R., & Slingerland, J. M. (2017) Obesity and adverse breast cancer risk and outcome: Mechanistic insights and strategies for intervention. CA Cancer J Clin. 67(5), 378–397.
Regulski, M., Regulska, K., Prukała, W., Piotrowska, H., Stanisz, B., & Murias, M. (2016) COX-2 inhibitors: a novel strategy in the management of breast cancer. Drug Discov Today. 21(4), 598-615.
Rizzello CG, Nionelli L, Coda R, Gobbetti M. Synthesis of the cancer preventive peptide lunasin by lactic acid bacteria during sourdough fermentation. Nutr Cancer. 2012;64(1):111-120. doi:10.1080/01635581.2012.630159
Rosner, W. (2015) Free estradiol and sex hormone-binding globulin. Steroids, 99(Pt A), 113-6.
Rose-John, S. (2018) Interleukin-6 Family Cytokines. Cold Spring Harb Perspect Biol. 1, 10(2). pii:a028415.
Saranya, C., Gauri, J. S., Timothy, H., & Angela, MH. B. (2011) Aromatase Inhibitors and Xenograft Studies. NIH Public Access Author Manuscript, 76(8), 730-735.
See Coppola S, Ghibelli L. GSH extrusion and the mitochondrial pathway of apoptotic signalling. Biochem Soc Trans. 2000;28:56–61 and references herein.
Shapira, N.(2017) The potential contribution of dietary factors to breast cancer prevention. Eur J Cancer Prev. 26(5), 385-395.
Shao, Z. M., Wu, J., Shen, Z. Z., & Barsky, S. H. (1998) Genistein exerts multiple suppressive effects on human breast carcinoma cells. Cancer Res. 1, 58(21), 4851-7.
Sheldon LA. Inhibition of E2F1 activity and cell cycle progression by arsenic via
retinoblastoma protein. Cell Cycle. 2017;16(21):2058-2072. doi:10.1080/15384101.2017.1338221
Shidal C, Inaba JI, Yaddanapudi K, Davis KR. The soy-derived peptide Lunasin inhibits invasive potential of melanoma initiating cells. Oncotarget. 2017;8(15):25525-25541. doi:10.18632/oncotarget.16066
Siegel, R. L., Miller, K. D. & Jemal, A. (2016) Cancer statistics. CA Cancer J Clin.66, 7-30.
Simpson, E. R., Clyne, C., Rubin, G., Boon, W. C., Robertson, K., Britt, K., Speed,C., & Jones, M. (2002) Aromatase-a brief overview. Annual Review of Physiology, 64, 93-127.
Singh BP, Vij S, Hati S. Functional significance of bioactive peptides derived from soybean. Peptides. 2014;54:171-179. doi:10.1016/j.peptides.2014.01.022
Spicer, D.V., Pike, M.C. Breast cancer prevention through modulation of endogenous hormones. (1993) Breast Cancer Res Tr 28, 179–193.
Su, B., Díaz-Cruz, E. S., Landini, S., & Brueggemeier, R. W. (2008) Suppression of aromatase in human breast cells by a cyclooxygenase-2 inhibitor and its analog involves multiple mechanisms independent of cyclooxygenase-2 inhibition. Steroids, 73(1), 104-11.
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), 356-65.
Sun, X., Zhang, J., Wang, Z., Ji, W., Tian, R., Zhang, F., & Niu, R. (2017) Shp2 Plays a Critical Role in IL-6-Induced EMT in Breast Cancer Cells. Int J Mol Sci. 13, 18(2).
Tanaka, T., Narazaki, M., & Kishimoto, T. (2014) IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol. 4, 6(10), a016295.
Te-Chi Hsieh & Lih-Chi Chen. (2010) The Evolution of Breast Cancer Treatment. Data Source Taipei City Medical Journal. 7(3), 313 – 322
Tian JM, Ran B, Zhang CL, Yan DM, Li XH. Estrogen and progesterone promote breast cancer cell proliferation by inducing cyclin G1 expression. Braz J Med Biol Res. 2018;51(3):1-7. Published 2018 Jan 23. doi:10.1590/1414-431X20175612
To, S. Q., Knower K. C., Cheung V., Simpson, E. R., & Clyne, C. D. (2015) Transcriptional control of local estrogen formation by aromatase in the breast. The Journal of Steroid Biochemistry and Molecular Biology, 145, 179-186.
Torre, L. A., Islami, F., Siegel, R. L., & Ward, E. M. (2017) Jemal AGlobal Cancer in Women: Burden and Trends. Cancer Epidemiology, Biomarkers & Prevention, 26(4), 444-457.
Valachovicova, T., Slivova, V., Bergman, H., Shuherk, J., & Sliva, D. (2004) Soy isoflavones suppress invasiveness of breast cancer cells by the inhibition of NF-kappaB/AP-1-dependent and -independent pathways. Int J Oncol. 25(5), 1389-95.
Victoria, M. G., Rexford, S. A., & Julia, T. (2016) Obesity and Breast Cancer: A Complex Relationship. Current Surgery Reports, 4, 14.
Vuyyuri, S. B., Shidal, C., Davis, K. R. (2018) Development of the plant-derived peptide lunasin as an anticancer agent. Curr Opin Pharmacol. 41, 27-33.
Wan, X., Liu, H., Sun, Y., Zhang, J., Chen, X., & Chen, N. (2017) Lunasin: A promising polypeptide for the prevention and treatment of cancer. Oncol Lett. 13(6), 3997-4001.
Wang, X., Simpson, E. R., & Brown, K. A. (2015) Aromatase overexpression in dysfunctional adipose tissue links obesity to postmenopausal breast cancer. The Journal of Steroid Biochemistry and Molecular Biology, 153, 35-44.
Wei Q, Liang X, Peng Y, et al. 17β-estradiol ameliorates oxidative stress and blue light-emitting diode-induced retinal degeneration by decreasing apoptosis and enhancing autophagy. Drug Des Devel Ther. 2018;12:2715-2730. Published 2018 Sep 4. doi:10.2147/DDDT.S176349
Wilkins, Robert H. (1992) [First published 1965]. Neurosurgical Classics (2nd ed.). Park Ridge, Illinois: American Association of Neurological Surgeons. ISBN 978-1-879284-09-8. LCCN 2011293270.
Xiaoling Puyang, Craig Furman, Guo Zhu Zheng, Zhenhua J. Wu, Deepti Banka, Kiran Aithal, Sergei Agoulnik, David M. Bolduc, Silvia Buonamici, Benjamin Caleb, Subhasree Das, Sean Eckley, Peter Fekkes, Ming-Hong Hao, Andrew Hart, René Houtman, Sean Irwin, Jaya J. Joshi, Craig Karr, Amy Kim, Namita Kumar, Pavan Kumar, Galina Kuznetsov, Weidong G. Lai, Nicholas Larsen, Crystal Mackenzie, Lesley-Ann Martin, Diana Melchers, Alyssa Moriarty, Tuong-Vi Nguyen, John Norris, Morgan O'Shea, Sunil Pancholi, Sudeep Prajapati, Sujatha Rajagopalan, Dominic J. Reynolds, Victoria Rimkunas, Nathalie Rioux, Ricardo Ribas, Amy Siu, Sasirekha Sivakumar, Vanitha Subramanian, Michael Thomas, Frédéric H. Vaillancourt, John Wang, Suzanne Wardell, Michael J. Wick, Shihua Yao, Lihua Yu, Markus Warmuth, Peter G. Smith, Ping Zhu and Manav Korpal. (2018) Discovery of Selective Estrogen Receptor Covalent Antagonists for the Treatment of ERαWT and ERαMUT Breast Cancer, Cancer Discov, 76-1193.
Yang X, Zhu J, Tung CY, et al. Lunasin alleviates allergic airway inflammation while increases antigen-specific Tregs. PLoS One. 2015;10(2):e0115330. Published 2015 Feb 3. doi:10.1371/journal.pone.0115330
Yin, R., Li, T., Tian, J. X., Xi, P., & Liu, R. H. (2018) Ursolic acid, a potential anticancer compound for breast cancer therapy. Crit Rev Food Sci Nutr. 4, 58(4),568-574.
Yoshikawa M, Fujita H, Matoba N, et al. Bioactive peptides derived from food proteins preventing lifestyle-related diseases. Biofactors. 2000;12(1-4):143-146. doi:10.1002/biof.5520120122
Zhang W, Hao Y, Teng C, et al. Effects of Salt Stimulation on Lunasin Accumulation and Activity during Soybean Germination. Foods. 2020;9(2):118.
Zhao, A. Z., Zhao, H., Teague, J., Fujimoto, W., & Beavo, J. A. (1997) Attenuation of insulin secretion by insulin-like growth factor 1 is mediated through activation of phosphodiesterase 3B. Proceedings of the National Academy of Sciences of the United States of America, 94(7), 3223-8.
Zhao, Q., Zhang, X., Cai, H., Zhang, P., Kong, D., Ge, X., Du, M., Liang, R., & Dong, W. (2018) Anticancer effects of plant derived Anacardic acid on human breast cancer MDA-MB-231 cells. Am J Transl Res. 15, 10(8), 2424-2434
Ziaei, S., & Halaby, R. (2017) Dietary Isoflavones and Breast Cancer Risk. Medicines (Basel). 7, 4(2).