研究生: |
陳晴盈 Chen, Ching-Ying |
---|---|
論文名稱: |
透過生物資訊學探討Ferroptosis在人類大腸直腸癌細胞中植化素Withaferin A合併鉑金類抗癌藥物的角色 The role of Ferroptosis in the combination treatment of Withaferin A and platinum anticancer agent in human colorectal cancer cells via bioinformatics analysis |
指導教授: |
蘇純立
Su, Chun-Li |
口試委員: |
蘇純立
Su, Chun-Li 黃奇英 Huang, Chi-Ying 劉校生 Liu, Hsiao-Sheng 蕭寧馨 Shaw, Ning-Shin |
口試日期: | 2024/07/04 |
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: | 2024 |
畢業學年度: | 112 |
語文別: | 中文 |
論文頁數: | 115 |
中文關鍵詞: | Ferroptosis 、大腸直腸癌 、Cisplatin 、Withaferin A 、Ferritinophagy |
英文關鍵詞: | Ferroptosis, Colorectal cancer, Cisplatin, Withaferin A, Ferritinophagy |
研究方法: | 實驗設計法 |
DOI URL: | http://doi.org/10.6345/NTNU202401461 |
論文種類: | 學術論文 |
相關次數: | 點閱:80 下載:1 |
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 |
在大腸直腸癌(Colorectal cancer,CRC)中,鉑金類藥物Cisplatin(Cis)的藥物不敏感與副作用的特性已成為十分嚴重問題。鐵依賴型細胞死亡(Ferroptosis)是透過增加細胞內游離鐵堆積並促進脂質過氧化物生成所導致的新型態細胞死亡機制。透過生物資訊學分析結果發現Cis藥物阻抗的CRC患者體內較藥物敏感的患者具有鐵代謝失調的問題。CRC組織較其他癌症組織有堆積較多二價鐵離子的潛力,並且CRC組織相較於正常組織有累積較多游離鐵與促進脂質過氧化物形成的特性,因此透過二價游離鐵促進細胞活性氧物質生成與降低抗氧化能力來誘導Ferroptosis將有機會改善CRC較低的無復發存活率。此外,相較於HCT116,Ferroptosis促進劑RSL3在HT-29中能引起更高的生長抑制作用,並且可以被Ferroptosis抑制劑Ferrostatin-1和Deferoxamine逆轉細胞生長抑制。同時HT-29中有較低的出鐵蛋白表現,代表細胞中可透過增加細胞內游離鐵來促進Ferroptosis。生物資訊學分析結果發現南非醉茄的酯類成分Withaferin A(WA)具有誘導Ferroptosis的潛力,並且在CRC中WA較Cis有較佳的藥物敏感性。合併Cis與WA能夠促進HT-29進行Ferroptosis相關生長抑制、脂質過氧化物累積、游離鐵累積與降低GPX4蛋白表現。此外,合併Cis與WA能增加shGFP HT-29的細胞生長抑制與促進ferritin與LC3B蛋白共位的情形,而這些結果在加入合併藥物的shATG5 HT-29會被抑制,代表Cis與WA可以增加細胞進行ferrtinophagy。綜合以上結果,本研究利用生物資訊學與實驗數據證實在CRC中植化素WA合併Cis能產生協同作用並促進Ferroptosis。
Drug resistance and side effect in Cisplatin (Cis) had become a serious problem in colorectal cancer (CRC). Ferroptosis is an iron-dependent regulated cell death caused by toxic lipid peroxidation. Through bioinformatics analysis, we discovered that Cis-resistant CRC patients exhibit iron metabolism disorders compared to the Cis-sensitive patients. Besides, CRC tissues, in contrast to other cancer tissues and normal tissues near by the CRC, tended to accumulate Fe2+ and promote lipid peroxidation. Therefore, inducing ferroptosis by increasing intracellular Fe2+ and reducing antioxidant capacity may improve the low relapse-free survival rate in CRC. Compared to HCT116, ferroptosis inducer RSL3 induced a higher growth inhibition in HT-29, and the growth inhibition was reduced by ferroptosis inhibitor Ferrostatin-1 and Deferoxamine. This observation is associated with a lower ferroportin in HT-29, indicating that increasing labile iron pool can promote Ferroptosis in HT-29. By analyzing the transcriptomics data, natural compound Withaferin A (WA) derived from Withania somnifera has the potential to induce Ferroptosis, and WA exhibits better drug sensitivity in CRC compared to Cis. Combination of Cis and WA-induced Ferroptosis in HT-29 was characterized by increasing growth inhibition and repressing GPX4 protein expression, also increasing lipid peroxides and cellular Fe2+ accumulation. Furthermore, the combination of Cis and WA increased growth inhibition and promoted the colocalization of ferritin and LC3B in shGFP HT-29 cells, while these effects were suppressed in Cis and WA treated shATG 5 HT-29 cells, indicating that Cis and WA enhanced ferritinophagy in HT-29 cells. Collectively, our unique integrated screening results and experimental data support the combination of natural compound WA and Cisplatin in producing synergistic effects and inducing ferroptosis in CRC.
衛生福利部(2023)‧110年國人死因統計結果‧取自https://www.mohw.gov.tw/cp-16-70314-1.html
AH., K., F., A., R., M., & RC., G. (2020). Synergistic combinations of paclitaxel and withaferin A against human non-small cell lung cancer cells.
Alnuqaydan AM, R. B., Almutary AG, Chauhan SS. (2020). Synergistic antitumor effect of 5-fluorouracil and withaferin-A induces endoplasmic reticulum stress-mediated autophagy and apoptosis in colorectal cancer cells.
Brookes, M. J., Hughes, S., Turner, F. E., Reynolds, G., Sharma, N., Ismail, T., Berx, G., McKie, A. T., Hotchin, N., Anderson, G. J., Iqbal, T., & Tselepis, C. (2006). Modulation of iron transport proteins in human colorectal carcinogenesis. Gut, 55(10), 1449-1460. https://doi.org/10.1136/gut.2006.094060
Bungau, S., Vesa, C. M., Abid, A., Behl, T., Tit, D. M., Purza, A. L., Pasca, B., Todan, L. M., & Endres, L. (2021). Withaferin A-A Promising Phytochemical Compound with Multiple Results in Dermatological Diseases. Molecules, 26(9). https://doi.org/10.3390/molecules26092407
Chaudhary, N., Choudhary, B. S., Shah, S. G., Khapare, N., Dwivedi, N., Gaikwad, A., Joshi, N., Raichanna, J., Basu, S., Gurjar, M., P, K. S., Saklani, A., Gera, P., Ramadwar, M., Patil, P., Thorat, R., Gota, V., Dhar, S. K., Gupta, S., Das, M., & Dalal, S. N. (2021). Lipocalin 2 expression promotes tumor progression and therapy resistance by inhibiting ferroptosis in colorectal cancer. Int J Cancer, 149(7), 1495-1511. https://doi.org/10.1002/ijc.33711
Chen, P., Li, X., Zhang, R., Liu, S., Xiang, Y., Zhang, M., Chen, X., Pan, T., Yan, L., Feng, J., Duan, T., Wang, D., Chen, B., Jin, T., Wang, W., Chen, L., Huang, X., Zhang, W., Sun, Y., Li, G., Kong, L., Chen, X., Li, Y., Yang, Z., Zhang, Q., Zhuo, L., Sui, X., & Xie, T. (2020). Combinative treatment of beta-elemene and cetuximab is sensitive to KRAS mutant colorectal cancer cells by inducing ferroptosis and inhibiting epithelial-mesenchymal transformation. Theranostics, 10(11), 5107-5119. https://doi.org/10.7150/thno.44705
Chen, W. C., Wang, C. Y., Hung, Y. H., Weng, T. Y., Yen, M. C., & Lai, M. D. (2016). Systematic Analysis of Gene Expression Alterations and Clinical Outcomes for Long-Chain Acyl-Coenzyme A Synthetase Family in Cancer. PLoS One, 11(5), e0155660. https://doi.org/10.1371/journal.pone.0155660
Chen, X., Kang, R., Kroemer, G., & Tang, D. (2021). Broadening horizons: the role of ferroptosis in cancer. Nat Rev Clin Oncol, 18(5), 280-296. https://doi.org/10.1038/s41571-020-00462-0
Chen, X., Zhu, N., Wu, Y., Zhang, Y., Zhang, Y., Jin, K., Zhou, Z., Chen, G., & Wang, J. (2024). Withaferin A, a natural thioredoxin reductase 1 (TrxR1) inhibitor, synergistically enhances the antitumor efficacy of sorafenib through ROS-mediated ER stress and DNA damage in hepatocellular carcinoma cells. Phytomedicine, 128, 155317. https://doi.org/10.1016/j.phymed.2023.155317
Chen, Y., Fan, Z., Yang, Y., & Gu, C. (2019). Iron metabolism and its contribution to cancer (Review). Int J Oncol, 54(4), 1143-1154. https://doi.org/10.3892/ijo.2019.4720
Chien, T. M., Wu, K. H., Chuang, Y. T., Yeh, Y. C., Wang, H. R., Yeh, B. W., Yen, C. H., Yu, T. J., Wu, W. J., & Chang, H. W. (2021). Withaferin A Triggers Apoptosis and DNA Damage in Bladder Cancer J82 Cells through Oxidative Stress. Antioxidants (Basel), 10(7). https://doi.org/10.3390/antiox10071063
Chua, A. C., Klopcic, B., Lawrance, I. C., Olynyk, J. K., & Trinder, D. (2010). Iron: an emerging factor in colorectal carcinogenesis. World J Gastroenterol, 16(6), 663-672. https://doi.org/10.3748/wjg.v16.i6.663
Cohen, S. M., Mukerji, R., Timmermann, B. N., Samadi, A. K., & Cohen, M. S. (2012). A novel combination of withaferin A and sorafenib shows synergistic efficacy against both papillary and anaplastic thyroid cancers. Am J Surg, 204(6), 895-900; discussion 900-891. https://doi.org/10.1016/j.amjsurg.2012.07.027
Dai, G., Wang, D., Ma, S., Hong, S., Ding, K., Tan, X., & Ju, W. (2022). ACSL4 promotes colorectal cancer and is a potential therapeutic target of emodin. Phytomedicine, 102, 154149. https://doi.org/10.1016/j.phymed.2022.154149
Devabattula, G., Panda, B., Yadav, R., & Godugu, C. (2024). The Potential Pharmacological Effects of Natural Product Withaferin A in Cancer: Opportunities and Challenges for Clinical Translation. Planta Med, 90(6), 440-453. https://doi.org/10.1055/a-2289-9600
Doll, S., Proneth, B., Tyurina, Y. Y., Panzilius, E., Kobayashi, S., Ingold, I., Irmler, M., Beckers, J., Aichler, M., Walch, A., Prokisch, H., Trumbach, D., Mao, G., Qu, F., Bayir, H., Fullekrug, J., Scheel, C. H., Wurst, W., Schick, J. A., Kagan, V. E., Angeli, J. P., & Conrad, M. (2017). ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition. Nat Chem Biol, 13(1), 91-98. https://doi.org/10.1038/nchembio.2239
Estevao, D., da Cruz-Ribeiro, M., Cardoso, A. P., Costa, A. M., Oliveira, M. J., Duarte, T. L., & da Cruz, T. B. (2023). Iron metabolism in colorectal cancer: a balancing act. Cell Oncol (Dordr), 46(6), 1545-1558. https://doi.org/10.1007/s13402-023-00828-3
Florea, A. M., & Busselberg, D. (2011). Cisplatin as an anti-tumor drug: cellular mechanisms of activity, drug resistance and induced side effects. Cancers (Basel), 3(1), 1351-1371. https://doi.org/10.3390/cancers3011351
Galluzzi, L., Senovilla, L., Vitale, I., Michels, J., Martins, I., Kepp, O., Castedo, M., & Kroemer, G. (2012). Molecular mechanisms of cisplatin resistance. Oncogene, 31(15), 1869-1883. https://doi.org/10.1038/onc.2011.384
Gao, M., Monian, P., Pan, Q., Zhang, W., Xiang, J., & Jiang, X. (2016). Ferroptosis is an autophagic cell death process. Cell Res, 26(9), 1021-1032. https://doi.org/10.1038/cr.2016.95
Ge, C., Zhang, S., Mu, H., Zheng, S., Tan, Z., Huang, X., Xu, C., Zou, J., Zhu, Y., Feng, D., & Aa, J. (2021). Emerging Mechanisms and Disease Implications of Ferroptosis: Potential Applications of Natural Products. Front Cell Dev Biol, 9, 774957. https://doi.org/10.3389/fcell.2021.774957
Guo, J., Xu, B., Han, Q., Zhou, H., Xia, Y., Gong, C., Dai, X., Li, Z., & Wu, G. (2018). Ferroptosis: A Novel Anti-tumor Action for Cisplatin. Cancer Res Treat, 50(2), 445-460. https://doi.org/10.4143/crt.2016.572
Han, S., Yang, X., Zhuang, J., Zhou, Q., Wang, J., Ru, L., Niu, F., & Mao, W. (2024). α-Hederin promotes ferroptosis and reverses cisplatin chemoresistance in non-small cell lung cancer.
Hassannia, B., Wiernicki, B., Ingold, I., Qu, F., Van Herck, S., Tyurina, Y. Y., Bayir, H., Abhari, B. A., Angeli, J. P. F., Choi, S. M., Meul, E., Heyninck, K., Declerck, K., Chirumamilla, C. S., Lahtela-Kakkonen, M., Van Camp, G., Krysko, D. V., Ekert, P. G., Fulda, S., De Geest, B. G., Conrad, M., Kagan, V. E., Vanden Berghe, W., Vandenabeele, P., & Vanden Berghe, T. (2018). Nano-targeted induction of dual ferroptotic mechanisms eradicates high-risk neuroblastoma. J Clin Invest, 128(8), 3341-3355. https://doi.org/10.1172/JCI99032
He, G., He, G., Zhou, R., Pi, Z., Zhu, T., Jiang, L., & Xie, Y. (2016). Enhancement of cisplatin-induced colon cancer cells apoptosis by shikonin, a natural inducer of ROS in vitro and in vivo. Biochem Biophys Res Commun, 469(4), 1075-1082. https://doi.org/10.1016/j.bbrc.2015.12.100
Horniblow, R. D., Bedford, M., Hollingworth, R., Evans, S., Sutton, E., Lal, N., Beggs, A., Iqbal, T. H., & Tselepis, C. (2017). BRAF mutations are associated with increased iron regulatory protein-2 expression in colorectal tumorigenesis. Cancer Sci, 108(6), 1135-1143. https://doi.org/10.1111/cas.13234
Hou, W., Xie, Y., Song, X., Sun, X., Lotze, M. T., Zeh, H. J., 3rd, Kang, R., & Tang, D. (2016). Autophagy promotes ferroptosis by degradation of ferritin. Autophagy, 12(8), 1425-1428. https://doi.org/10.1080/15548627.2016.1187366
Huang, J., Chen, J., & Li, J. (2024). Quercetin promotes ATG5-mediating autophagy-dependent ferroptosis in gastric cancer. J Mol Histol, 55(2), 211-225. https://doi.org/10.1007/s10735-024-10186-5
Hur, J., Otegbeye, E., Joh, H. K., Nimptsch, K., Ng, K., Ogino, S., Meyerhardt, J. A., Chan, A. T., Willett, W. C., Wu, K., Giovannucci, E., & Cao, Y. (2021). Sugar-sweetened beverage intake in adulthood and adolescence and risk of early-onset colorectal cancer among women. Gut, 70(12), 2330-2336. https://doi.org/10.1136/gutjnl-2020-323450
Jiang, X., Stockwell, B. R., & Conrad, M. (2021). Ferroptosis: mechanisms, biology and role in disease. Nat Rev Mol Cell Biol, 22(4), 266-282. https://doi.org/10.1038/s41580-020-00324-8
Kakar, S. S., Jala, V. R., & Fong, M. Y. (2012). Synergistic cytotoxic action of cisplatin and withaferin A on ovarian cancer cell lines. Biochem Biophys Res Commun, 423(4), 819-825. https://doi.org/10.1016/j.bbrc.2012.06.047
Koberle, B., & Schoch, S. (2021). Platinum Complexes in Colorectal Cancer and Other Solid Tumors. Cancers (Basel), 13(9). https://doi.org/10.3390/cancers13092073
Kyakulaga, A. H., Aqil, F., Munagala, R., & Gupta, R. C. (2018). Withaferin A inhibits Epithelial to Mesenchymal Transition in Non-Small Cell Lung Cancer Cells. Sci Rep, 8(1), 15737. https://doi.org/10.1038/s41598-018-34018-1
Lin, P. L., Tang, H. H., Wu, S. Y., Shaw, N. S., & Su, C. L. (2020). Saponin Formosanin C-induced Ferritinophagy and Ferroptosis in Human Hepatocellular Carcinoma Cells. Antioxidants (Basel), 9(8). https://doi.org/10.3390/antiox9080682
Ma, M. Z., Chen, G., Wang, P., Lu, W. H., Zhu, C. F., Song, M., Yang, J., Wen, S., Xu, R. H., Hu, Y., & Huang, P. (2015). Xc- inhibitor sulfasalazine sensitizes colorectal cancer to cisplatin by a GSH-dependent mechanism. Cancer Lett, 368(1), 88-96. https://doi.org/10.1016/j.canlet.2015.07.031
Manz, D. H., Blanchette, N. L., Paul, B. T., Torti, F. M., & Torti, S. V. (2016). Iron and cancer: recent insights. Ann N Y Acad Sci, 1368(1), 149-161. https://doi.org/10.1111/nyas.13008
Miotto, G., Rossetto, M., Di Paolo, M. L., Orian, L., Venerando, R., Roveri, A., Vuckovic, A. M., Bosello Travain, V., Zaccarin, M., Zennaro, L., Maiorino, M., Toppo, S., Ursini, F., & Cozza, G. (2020). Insight into the mechanism of ferroptosis inhibition by ferrostatin-1. Redox Biol, 28, 101328. https://doi.org/10.1016/j.redox.2019.101328
Mármol, I., Sánchez-de-Diego, C., Pradilla Dieste, A., Cerrada, E., & Rodriguez Yoldi, M. (2017). Colorectal Carcinoma: A General Overview and Future Perspectives in Colorectal Cancer. International Journal of Molecular Sciences, 18(1). https://doi.org/10.3390/ijms18010197
Osborne, N. J., Gurrin, L. C., Allen, K. J., Constantine, C. C., Delatycki, M. B., McLaren, C. E., Gertig, D. M., Anderson, G. J., Southey, M. C., Olynyk, J. K., Powell, L. W., Hopper, J. L., Giles, G. G., & English, D. R. (2010). HFE C282Y homozygotes are at increased risk of breast and colorectal cancer. Hepatology, 51(4), 1311-1318. https://doi.org/10.1002/hep.23448
Osman, A. M., Al-Malki, H. S., Al-Harthi, S. E., El-Hanafy, A. A., Elashmaoui, H. M., & Elshal, M. F. (2015). Modulatory role of resveratrol on cytotoxic activity of cisplatin, sensitization and modification of cisplatin resistance in colorectal cancer cells. Mol Med Rep, 12(1), 1368-1374. https://doi.org/10.3892/mmr.2015.3513
Pino, M. S., & Chung, D. C. (2010). The chromosomal instability pathway in colon cancer. Gastroenterology, 138(6), 2059-2072. https://doi.org/10.1053/j.gastro.2009.12.065
Rajkumar, P., Mathew, B. S., Das, S., Isaiah, R., John, S., Prabha, R., & Fleming, D. H. (2016). Cisplatin Concentrations in Long and Short Duration Infusion: Implications for the Optimal Time of Radiation Delivery. J Clin Diagn Res, 10(7), XC01-XC04. https://doi.org/10.7860/JCDR/2016/18181.8126
Sehm, T., Rauh, M., Wiendieck, K., Buchfelder, M., Eyüpoglu, I. Y., & Savaskan, N. E. (2016). Temozolomide toxicity operates in a xCT SLC7a11 dependent manner and is fostered by ferroptosis.pdf.
Sharma, S., Joshi, A., & Hemalatha, S. (2017). Protective Effect of Withania coagulans Fruit Extract on Cisplatin-induced Nephrotoxicity in Rats. Pharmacognosy Res, 9(4), 354-361. https://doi.org/10.4103/pr.pr_1_17
Sornjai, W., Nguyen Van Long, F., Pion, N., Pasquer, A., Saurin, J. C., Marcel, V., Diaz, J. J., Mertani, H. C., & Smith, D. R. (2020). Iron and hepcidin mediate human colorectal cancer cell growth. Chem Biol Interact, 319, 109021. https://doi.org/10.1016/j.cbi.2020.109021
Sui, X., Zhang, R., Liu, S., Duan, T., Zhai, L., Zhang, M., Han, X., Xiang, Y., Huang, X., Lin, H., & Xie, T. (2018). RSL3 Drives Ferroptosis Through GPX4 Inactivation and ROS Production in Colorectal Cancer. Front Pharmacol, 9, 1371. https://doi.org/10.3389/fphar.2018.01371
Tang, D., Chen, X., Kang, R., & Kroemer, G. (2021). Ferroptosis: molecular mechanisms and health implications. Cell Res, 31(2), 107-125. https://doi.org/10.1038/s41422-020-00441-1
Thanikachalam, K., & Khan, G. (2019). Colorectal Cancer and Nutrition. Nutrients, 11(1). https://doi.org/10.3390/nu11010164
Torti, S. V., & Torti, F. M. (2013). Iron and cancer: more ore to be mined. Nat Rev Cancer, 13(5), 342-355. https://doi.org/10.1038/nrc3495
Vyas, A. R., & Singh, S. V. (2014). Molecular targets and mechanisms of cancer prevention and treatment by withaferin a, a naturally occurring steroidal lactone. AAPS J, 16(1), 1-10. https://doi.org/10.1208/s12248-013-9531-1
Wang, Y., Zhang, Z., Sun, W., Zhang, J., Xu, Q., Zhou, X., & Mao, L. (2022). Ferroptosis in colorectal cancer: Potential mechanisms and effective therapeutic targets. Biomed Pharmacother, 153, 113524. https://doi.org/10.1016/j.biopha.2022.113524
Wilson, M. J., Harlaar, J. J., Jeekel, J., Schipperus, M., & Zwaginga, J. J. (2018). Iron therapy as treatment of anemia: A potentially detrimental and hazardous strategy in colorectal cancer patients. Med Hypotheses, 110, 110-113. https://doi.org/10.1016/j.mehy.2017.12.011
Wu, J., Liao, Q., Zhang, L. I., Wu, S., & Liu, Z. (2023). TGF-beta-regulated different iron metabolism processes in the development and cisplatin resistance of ovarian cancer. Oncol Res, 32(2), 373-391. https://doi.org/10.32604/or.2023.031404
Xia, S., Miao, Y., & Liu, S. (2018). Withaferin A induces apoptosis by ROS-dependent mitochondrial dysfunction in human colorectal cancer cells. Biochem Biophys Res Commun, 503(4), 2363-2369. https://doi.org/10.1016/j.bbrc.2018.06.162
Xu, T., Ding, W., Ji, X., Ao, X., Liu, Y., Yu, W., & Wang, J. (2019). Molecular mechanisms of ferroptosis and its role in cancer therapy. J Cell Mol Med, 23(8), 4900-4912. https://doi.org/10.1111/jcmm.14511
Xu, X., Zhang, X., Wei, C., Zheng, D., Lu, X., Yang, Y., Luo, A., Zhang, K., Duan, X., & Wang, Y. (2020). Targeting SLC7A11 specifically suppresses the progression of colorectal cancer stem cells via inducing ferroptosis. Eur J Pharm Sci, 152, 105450. https://doi.org/10.1016/j.ejps.2020.105450
Yan, H., Talty, R., Jain, A., Cai, Y., Zheng, J., Shen, X., Muca, E., Paty, P. B., Bosenberg, M. W., Khan, S. A., & Johnson, C. H. (2023). Discovery of decreased ferroptosis in male colorectal cancer patients with KRAS mutations. Redox Biol, 62, 102699. https://doi.org/10.1016/j.redox.2023.102699
Yang, Y., Liu, L., Tian, Y., Gu, M., Wang, Y., Ashrafizadeh, M., Reza Aref, A., Canadas, I., Klionsky, D. J., Goel, A., Reiter, R. J., Wang, Y., Tambuwala, M., & Zou, J. (2024). Autophagy-driven regulation of cisplatin response in human cancers: Exploring molecular and cell death dynamics. Cancer Lett, 587, 216659. https://doi.org/10.1016/j.canlet.2024.216659
Ye, X., Zhou, X. J., & Zhang, H. (2018). Exploring the Role of Autophagy-Related Gene 5 (ATG5) Yields Important Insights Into Autophagy in Autoimmune/Autoinflammatory Diseases. Front Immunol, 9, 2334. https://doi.org/10.3389/fimmu.2018.02334
Zhang, X., Ma, Y., Ma, J., Yang, L., Song, Q., Wang, H., & Lv, G. (2022). Glutathione Peroxidase 4 as a Therapeutic Target for Anti-Colorectal Cancer Drug-Tolerant Persister Cells. Front Oncol, 12, 913669. https://doi.org/10.3389/fonc.2022.913669
Zhang, Y., Tan, Y., Liu, S., Yin, H., Duan, J., Fan, L., Zhao, X., & Jiang, B. (2023). Implications of Withaferin A for the metastatic potential and drug resistance in hepatocellular carcinoma cells via Nrf2-mediated EMT and ferroptosis. Toxicol Mech Methods, 33(1), 47-55. https://doi.org/10.1080/15376516.2022.2075297
Zhang, Z., Ji, Y., Hu, N., Yu, Q., Zhang, X., Li, J., Wu, F., Xu, H., Tang, Q., & Li, X. (2022). Ferroptosis-induced anticancer effect of resveratrol with a biomimetic nano-delivery system in colorectal cancer treatment. Asian J Pharm Sci, 17(5), 751-766. https://doi.org/10.1016/j.ajps.2022.07.006