Tetrandrine suppresses tumor growth and angiogenesis of gliomas in rats

Abstract

Tetrandrine, a bisbenzylisoquinoline alkaloid, has antitumor effects against some cancers, but its effects on gliomas are unknown. In this study, we investigated the effects of tetrandrine on the growth and angiogenesis of rat RT-2 gliomas. We treated RT-2 glioma cells with tetrandrine and then measured cytotoxicity, apoptosis and expression of vascular endothelial growth factor (VEGF). We also examined the cytotoxic effect of tetrandrine on the ECV304 human umbilical vein endothelial cells and the effects of tetrandrine on the in vivo angiogenesis. Tumor size and animal survival were followed in tetrandrine-treated rats with subcutaneous or intracerebral gliomas. Expression of CD31 in tetrandrinetreated gliomas was followed to study its effect on glioma-induced angiogenesis. Tetrandrine had cytotoxic effects and induced apoptosis of glioma cells in a concentration-and time-dependent manner. Tetrandrine also inhibited the expression of VEGF in glioma cells, induced cytotoxicity effect on the ECV304 cells and suppressed the in vivo angiogenesis. Tetrandrine (150 mg/kg/day) had significant antitumor effects on subcutaneous tumors and led to slower tumor growth rate, longer animal survival time and higher animal survival (p < 0.05). Tetrandrine also affected intracerebral tumors and prolonged animal survival (p < 0.05) without affecting survival rate. Immunohistochemical analyses showed that the subcutaneous gliomas from tetrandrine-treated rats had fewer microvessel densities than control rats (p 5 0.01). The results demonstrate that tetrandrine is cytotoxic to RT-2 glioma cells, has antitumor effects on subcutaneous and intracerebral gliomas, and inhibits angiogenesis in subcutaneous gliomas. Tetrandrine has potential as a treatment for gliomas.

Fangchinoline Inhibits Breast Adenocarcinoma Proliferation by Inducing Apoptosis

“…23) In the present study, we investigated the mechanism behind the antiproliferative effects of fangchinoline in breast cancer cells. Our study demonstrated that cancer cells treated with fangchinoline led to marked chromatin condensation and nuclear fragmentation, a biochemical hallmark of apoptosis.…”

Tetrandrine induces cell death in SAS human oral cancer cells through caspase activation-dependent apoptosis and LC3-I and LC3-II activation-dependent autophagy

“…Tetrandrine have been demonstrated to inhibit lipid peroxidation and platelet aggregation and reduces ischemia/reperfusion injury (28)(29)(30) and tetrandrine suppressed T and B cells and inhibited the production of cytokines (29). It was reported that tetrandrine is cytotoxic to RT-2 glioma cells and it has antitumor effects on subcutaneous and intracerebral gliomas, and inhibits angiogenesis in subcutaneous gliomas (31)(32)(33)(34). Tetradine induced apoptosis by activating reactive oxygen species and repressing Akt activity in human hepatocellular carcinoma HCC cells (35,36).…”

Tetrandrine Inhibits Wnt/β-Catenin Signaling and Suppresses Tumor Growth of Human Colorectal Cancer

“…Recent studies indicate that TET exhibits anti-inflammatory and anticancer activity (Xu et al, 2006;Liu et al, 2008;Chen et al, 2009;Wu et al, 2010). It has been reported that TET may target regulatory signaling pathways that are involved in cell cycling and cytotoxicity (Lee et al, 2002;Meng et al, 2004;Ng et al, 2006).…”