Huachansu suppresses human bladder cancer cell growth through the Fas/Fasl and TNF- alpha/TNFR1 pathway in vitro and in vivo

详细信息    查看全文

• 作者：Tao Yang (1)
  Runlin Shi (1)
  Lei Chang (2)
  Kun Tang (1)
  Ke Chen (1)
  Gan Yu (1)
  Yuanfeng Tian (1)
  Yonglian Guo (2)
  Wei He (1)
  Xiaodong Song (1)
  Hua Xu (1)
  Zhangqun Ye (1)
  
  1. Department and Institute of Urology ; Tongji Hospital ; Tongji Medical College ; Huazhong University of Science and Technology ; Wuhan ; 430030 ; China
  2. Department of Urology ; Central Hospital of Wuhan ; Wuhan ; 430014 ; China
  
• 关键词：Huachansu ; Bladder cancer ; Apoptosis ; TNF ; alpha/TNFR1 ; Fas/Fasl
• 刊名：Journal of Experimental & Clinical Cancer Research
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：34
• 期：1
• 全文大小：3,366 KB
• 参考文献：1. Bryan, RT (2011) Bladder cancer and cancer stem cells: basic science and implications for therapy. Sci World J 11: pp. 1187-94 CrossRef
  2. Arentsen, HC, Hendricksen, K, Oosterwijk, E, Witjes, JA (2009) Experimental rat bladder urothelial cell carcinoma models. World J Urol 27: pp. 313-7 CrossRef
  3. Shen, Z, Shen, T, Wientjes, MG, O'Donnell, MA, Au, JL (2008) Intravesical treatments of bladder cancer: review. Pharm Res 25: pp. 1500-10 CrossRef
  4. Schenk-Braat, EA, Bangma, CH (2005) Immunotherapy for superficial bladder cancer. Cancer Immunol Immun CII 54: pp. 414-23 CrossRef
  5. Gartrell, BA, Sonpavde, G (2013) Emerging drugs for urothelial carcinoma. Expert Opin Emerging Drugs 18: pp. 477-94 CrossRef
  6. Orang-Ojong, BB, Munyangaju, JE, Wei, MS, Lin, M, Wei, FG, Foukunang, C (2013) Impact of natural resources and research on cancer treatment and prevention: A perspective from Cameroon. Mol Clin Oncol 1: pp. 610-20
  7. Basmadjian, C, Zhao, Q, Bentouhami, E, Djehal, A, Nebigil, CG, Johnson, RA (2014) Cancer wars: natural products strike back. Frontiers Chem 2: pp. 20 CrossRef
  8. Qi, F, Li, A, Inagaki, Y, Kokudo, N, Tamura, S, Nakata, M (2011) Antitumor activity of extracts and compounds from the skin of the toad Bufo bufo gargarizans Cantor. Int Immunopharmacol 11: pp. 342-9 CrossRef
  9. Qi, F, Inagaki, Y, Gao, B, Cui, X, Xu, H, Kokudo, N (2011) Bufalin and cinobufagin induce apoptosis of human hepatocellular carcinoma cells via Fas- and mitochondria-mediated pathways. Cancer Sci 102: pp. 951-8 CrossRef
  10. Meng, Z, Yang, P, Shen, Y, Bei, W, Zhang, Y, Ge, Y (2009) Pilot study of huachansu in patients with hepatocellular carcinoma, nonsmall-cell lung cancer, or pancreatic cancer. Cancer 115: pp. 5309-18 CrossRef
  11. Ye, M, Guo, H, Guo, H, Han, J, Guo, D (2006) Simultaneous determination of cytotoxic bufadienolides in the Chinese medicine ChanSu by high-performance liquid chromatography coupled with photodiode array and mass spectrometry detections. J Chromatogr B Anal Technol Biomed Life Sci 838: pp. 86-95 CrossRef
  12. Watabe, M, Ito, K, Masuda, Y, Nakajo, S, Nakaya, K (1998) Activation of AP-1 is required for bufalin-induced apoptosis in human leukemia U937 cells. Oncogene 16: pp. 779-87 CrossRef
  13. Li, D, Qu, X, Hou, K, Zhang, Y, Dong, Q, Teng, Y (2009) PI3K/Akt is involved in bufalin-induced apoptosis in gastric cancer cells. Anti-Cancer Drugs 20: pp. 59-64 CrossRef
  14. Yu, CH, Kan, SF, Pu, HF, Jea Chien, E, Wang, PS (2008) Apoptotic signaling in bufalin- and cinobufagin-treated androgen-dependent and -independent human prostate cancer cells. Cancer Sci 99: pp. 2467-76 CrossRef
  15. Reis, LO, Ferreira, U, Billis, A, Cagnon, VH, Favaro, WJ (2012) Anti-angiogenic effects of the superantigen staphylococcal enterotoxin B and bacillus Calmette-Guerin immunotherapy for nonmuscle invasive bladder cancer. J Urol 187: pp. 438-45 CrossRef
  16. To, KK, Au-Yeung, SC, Ho, YP (2006) Differential nephrotoxicity of cisplatin and a novel series of traditional Chinese medicine-platinum anticancer agents correlates with their chemical reactivity towards sulfur-containing nucleophiles. Anti-Cancer Drugs 17: pp. 673-83 CrossRef
  17. Mehta, RG, Murillo, G, Naithani, R, Peng, X (2010) Cancer chemoprevention by natural products: how far have we come?. Pharm Res 27: pp. 950-61 CrossRef
  18. Nicholson, DW (1999) Caspase structure, proteolytic substrates, and function during apoptotic cell death. Cell Death Differ 6: pp. 1028-42 CrossRef
  19. Burkle, A, Brabeck, C, Diefenbach, J, Beneke, S (2005) The emerging role of poly(ADP-ribose) polymerase-1 in longevity. Int J Biochem Cell Biol 37: pp. 1043-53 CrossRef
  20. Yu, SW, Andrabi, SA, Wang, H, Kim, NS, Poirier, GG, Dawson, TM (2006) Apoptosis-inducing factor mediates poly(ADP-ribose) (PAR) polymer-induced cell death. Proc Natl Acad Sci U S A 103: pp. 18314-9 CrossRef
  21. Hunter, AM, LaCasse, EC, Korneluk, RG (2007) The inhibitors of apoptosis (IAPs) as cancer targets. Apoptosis Int J Program Cell Death 12: pp. 1543-68 CrossRef
  22. Heath-Engel, HM, Chang, NC, Shore, GC (2008) The endoplasmic reticulum in apoptosis and autophagy: role of the BCL-2 protein family. Oncogene 27: pp. 6419-33 CrossRef
  23. Huang, X, Lu, Z, Lv, Z, Yu, T, Yang, P, Shen, Y (2013) The Fas/Fas ligand death receptor pathway contributes to phenylalanine-induced apoptosis in cortical neurons. PLoS ONE 8: pp. e71553 CrossRef
  24. Ashkenazi, A (2002) Targeting death and decoy receptors of the tumour-necrosis factor superfamily. Nat Rev Cancer 2: pp. 420-30 CrossRef
  25. Shimada, K, Nakamura, M, Ishida, E, Kishi, M, Yonehara, S, Konishi, N (2003) c-Jun NH2-terminal kinase-dependent Fas activation contributes to etoposide-induced apoptosis in p53-mutated prostate cancer cells. Prostate 55: pp. 265-80 CrossRef
  26. Lavrik, IN, Krammer, PH (2012) Regulation of CD95/Fas signaling at the DISC. Cell Death Differ 19: pp. 36-41 CrossRef
  27. Kober, AM, Legewie, S, Pforr, C, Fricker, N, Eils, R, Krammer, PH (2011) Caspase-8 activity has an essential role in CD95/Fas-mediated MAPK activation. Cell Death Dis 2: pp. e212 CrossRef
  28. Aggarwal, BB (2003) Signalling pathways of the TNF superfamily: a double-edged sword. Nat Rev Immunol 3: pp. 745-56 CrossRef
  29. Bhardwaj, A, Aggarwal, BB (2003) Receptor-mediated choreography of life and death. J Clin Immunol 23: pp. 317-32 CrossRef
  30. Micheau, O, Tschopp, J (2003) Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes. Cell 114: pp. 181-90 CrossRef
  31. Beg, AA, Baltimore, D (1996) An essential role for NF-kappaB in preventing TNF-alpha-induced cell death. Science 274: pp. 782-4 CrossRef
  
• 刊物主题：Oncology; Cancer Research;
• 出版者：BioMed Central
• ISSN：1756-9966

文摘

Background Huachansu (HCS), a class of toxic steroids extracted from toad venom, which has been shown to be a valuable anticancer drug in many kinds of cancers. However, the effect of HCS on bladder cancer has not been elucidated. In this study, we focused on the antitumor activities and related mechanisms of HCS on bladder cancer in vitro and in vivo. Methods Cell viability of T24, EJ, RT-4, SV-HUC-1 cells after HCS treatment was measured by MTS, whereas the changes of cell morphology were observed by transmission electron microscopy. The early apoptosis induced by HCS was evaluated by flow cytometry, and the expression level of apoptosis-related molecules (Bax, Bcl-2, XIAP, PARP, cleaved-Caspases 3, 8, 9) was detected using Western blot. We then evaluated the impact of HCS on the expression of Fas/Fasl, TNF- alpha/TNFR1, and the activation of NF-Kappa B pathway, and furthermore the effect of these pathways in HCS induced-apoptosis were also detected. At last, xenograft tumor in nude mice was used to further investigate the antitumor effect of HCS in vivo. Results Our results showed that HCS could efficiently inhibit proliferation and induce apoptosis in human bladder cancer cell lines. The expression of Fas, Fasl, TNF- alpha were all elevated at both mRNA and protein level after HCS treatment. Furthermore, down regulation of TNF- alpha, TNFR1, Fas or inhibition of Fas/Fasl interaction decreased the relative number of death cells induced by HCS. In vivo, HCS treatment significantly suppressed tumor growth and induced apoptosis in xenografts tumor in nude mice. Conclusions HCS could efficiently inhibit proliferation and induce apoptosis in human bladder cancer cells in vitro and in vivo, which is largely mediated by Fas/Fasl and TNF- alpha/TNFR1 pathway.