Sensitization to TRAIL and Radioprotective Effect of NCoumaroyl Tyramine Diacetate from Tinospora Cordifolia Induces Apoptosis and Inhibits Neoangiogenesis to Act as an Anti-Cancer Compound
IOSR Journal of Biotechnology and Biochemistry
Tumor cells show differential sensitivity to cell death induced by TRAIL and also develop resistance to conventional radiation therapy along with several side effects being cytotoxic to normal cells. In this present study, we are focusing on tumor sensitization and radioprotective properties of a novel Phyto-compound isolated, purified from hexane extract and structurally identified as N-Coumaroyl tyramine diacetate (N-CTD), from T.cordifolia. We have isolated a novel small molecule
... d as N-coumaroyl tyramine diacetate from T. cordifolia. Trypan blue exclusion assay was used to study the tumor sensitization effect of N-CTD on TRAIL-resistant cells. The flow cytometric analysis was used to analyze the efficiency of N-CTD to induce apoptosis in TRAIL-resistant cells. To assess the radioprotective effect of N-CTD, the tumor-bearing mice were treated with N-CTD and irradiated with gamma radiation. The survival rate and its effect on peritoneal angiogenesis were studied. Pre-treatment with N-CTD sensitized TRAILresistant cells to TRAIL-mediated cell death. Flow cytometric analysis showed increased death in TRAIL-resistant cells upon combinatorial treatment. When a single dose of N-CTD combined with the sub-lethal dose of gamma radiation was initiated, the result showed a substantial decrease on peritoneal angiogenesis with increased survivability, decreased cell number and ascites volume in tumor-bearing mice treated with N-CTD. Further, the effect was studied in terms of MVD and presence of CD31 endothelial cell marker. The results were promising to prove that N-CTD is a potential small molecule with antiangiogenic, tumor sensitization and radioprotective effect; the same can be exploited for human applications.