Abstract
BackgroundHuachansu (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.MethodsCell 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.ResultsOur 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.ConclusionsHCS 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-015-0134-9) contains supplementary material, which is available to authorized users.
Highlights
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
We explored that HCS induces apoptosis in cell culture, and in tumor cells in vivo, as demonstrated in bladder cancer xenograft model treated with non-toxic dilutions of HCS
Taken together, our study demonstrated that HCS induced-apoptosis in human bladder cancer was mediated by the activation Fas/Fasl and TNF-α/Tumor necrosis factor receptor 1 (TNFR1)
Summary
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. We focused on the antitumor activities and related mechanisms of HCS on bladder cancer in vitro and in vivo. Huachansu (HCS) is an injectable form of chansu, the extract contains several biologically active substances, primarily indole alkaloids (bufotenine, bufotenidine, and cinobufotenine) and steroidal cardiac glycosides (bufalin, resibufogenin, cinobufagin, cinobufotalin, marinobufagin, and bufotalin). Recent studies showed that the antitumor activity of HCS can be attributed mainly to the cardiac glycosides it contains, including bufalin, resibufogenin, and cinobufagin. We investigated the anticancer effects and related molecular mechanisms of HCS on bladder cancer in vitro and in vivo
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