Waltonitone induces apoptosis through mir-663-induced Bcl-2 downregulation in non-small cell lung cancer

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• 作者：Yi Zhang ; Xiao Zhou ; Xiaoman Xu ; Meng Zhang ; Xin Wang ; Xue Bai ; Hui Li…
• 关键词：Waltonitone ; Lung cancer ; Apoptosis ; miR ; 663
• 刊名：Tumor Biology
• 出版年：2015
• 出版时间：February 2015
• 年：2015
• 卷：36
• 期：2
• 页码：871-876
• 全文大小：565 KB
• 参考文献：1. Travis, WD (2002) Pathology of lung cancer. Clin Chest Med 23: pp. 65-81 CrossRef
  2. Jemal, A, Siegel, R, Ward, E, Hao, Y, Xu, J, Thun, MJ (2009) Cancer statistics, 2009. CA Cancer J Clin 59: pp. 225-49 CrossRef
  3. Minna, JD, Roth, JA, Gazdar, AF (2002) Focus on lung cancer. Cancer Cell 1: pp. 49-52 CrossRef
  4. Schiller, JH, Harrington, D, Belani, CP, Langer, C, Sandler, A, Krook, J (2002) Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 346: pp. 92-8 CrossRef
  5. Chen, HY, Yu, SL, Chen, CH, Chang, GC, Chen, CY, Yuan, A (2007) A five-gene signature and clinical outcome in non-small-cell lung cancer. N Engl J Med 356: pp. 11-20 CrossRef
  6. O'Mahony, D, Kummar, S, Gutierrez, ME (2005) Non-small-cell lung cancer vaccine therapy: a concise review. J Clin Oncol 23: pp. 9022-8 CrossRef
  7. Zhang, Z, Wang, S, Qiu, H, Duan, C, Ding, K, Wang, Z (2009) Waltonitone induces human hepatocellular carcinoma cells apoptosis in vitro and in vivo. Cancer Lett 286: pp. 223-31 CrossRef
  8. Zhang, Y, Zhang, GB, Xu, XM, Zhang, M, Qu, D, Niu, HY (2012) Suppression of growth of A549 lung cancer cells by waltonitone and its mechanisms of action. Oncol Rep 28: pp. 1029-35
  9. Tili, E, Michaille, JJ, Alder, H, Volinia, S, Delmas, D, Latruffe, N (2010) Resveratrol modulates the levels of microRNAs targeting genes encoding tumor-suppressors and effectors of TGFbeta signaling pathway in SW480 cells. Biochem Pharmacol 80: pp. 2057-65 CrossRef
  10. Pan, J, Hu, H, Zhou, Z, Sun, L, Peng, L, Yu, L (2010) Tumor-suppressive mir-663 gene induces mitotic catastrophe growth arrest in human gastric cancer cells. Oncol Rep 24: pp. 105-12
  11. Massague, J (2008) TGFbeta in Cancer. Cell 134: pp. 215-30 CrossRef
  12. Tian, M, Schiemann, WP (2009) The TGF-beta paradox in human cancer: an update. Future Oncol 5: pp. 259-71 CrossRef
  13. Tili, E, Michaille, JJ, Adair, B, Alder, H, Limagne, E, Taccioli, C (2010) Resveratrol decreases the levels of miR-155 by upregulating miR-663, a microRNA targeting JunB and JunD. Carcinogenesis 31: pp. 1561-6 CrossRef
  14. Lin, X, Guan, H, Huang, Z, Liu, J, Li, H, Wei, G (2014) Downregulation of Bcl-2 expression by miR-34a mediates palmitate-induced Min6 cells apoptosis. J Diabetes Res 2014: pp. 258695
  15. Pareja, F, Macleod, D, Shu, C, Crary, JF, Canoll, PD, Ross, AH (2014) PI3K and Bcl-2 inhibition primes glioblastoma cells to apoptosis through downregulation of Mcl-1 and phospho-BAD. Mol Cancer Res 12: pp. 987-1001 CrossRef
  16. Hu, CJ, Zhou, L, Cai, Y (2014) Dihydroartemisinin induces apoptosis of cervical cancer cells via upregulation of RKIP and downregulation of Bcl-2. Cancer Biol Ther 15: pp. 279-88 CrossRef
  
• 刊物主题：Cancer Research;
• 出版者：Springer Netherlands
• ISSN：1423-0380

文摘

Our previous study reported that waltonitone treatment inhibited proliferation and induced apoptosis of lung cancer cells. However, the mechanism of waltonitone-induced toxicity remains unclear. In the present study, we treated H460 and H3255 lung cancer cells using different concentration of waltonitone (0, 10, 20, 30?μmol/L). We observed that waltonitone inhibited cell viability and induced apoptosis in a concentration dependent manner, with upregulation of caspase-3 cleavage. We also observed upregulation of miR-663, a potential tumor suppressor, after waltonitone treatment. Suppression of miR-663 function using miR-663 inhibitor partly alleviated cell toxicity induced by waltonitone. In addition, both waltonitone treatment and transfection of miR-663 mimic upregulated Bcl-2 mRNA and protein expression. Bcl-2 transfection alleviated waltonitone-induced toxicity. Furthermore, transfection of miR-663 inhibitor upregulated Bcl-2 levels in both cell lines. In summary, the present study demonstrated that waltonitone induced apoptosis of lung cancer cells through, at least partly, miR-663-induced Bcl-2 downregulation.