Trichosanthin-induced autophagy in gastric cancer cell MKN-45 is dependent on reactive oxygen species (ROS) and NF-κB/p53 pathway

Trichosanthin (tcs),isolated from the root tuber of trichosanthes kirilowii tubers in the cucurbitaceae family,owns a great deal of biological and pharmacological activities including anti-virus and anti-tumor. tcs has been reported to induce cell apoptosis of a diversity of cancers,including cervical cancer,choriocarcinoma,and gastric cancer,etc. however,whether tcs would induce autophagy in gastric cancer cells was seldom investigated. in current study,human gastric cancer mkn-45 cell growth was significantly inhibited by tcs. the anti-proliferation effect of tcs was due to an increased autophagy,which was confirmed by monodansylcadervarine (mdc) staining,up-regulation of autophagy protein 5 (atg5),and conversion of lc3 i to lc3 ii (autophagosome marker). in addition,tcs induced reactive oxygen species (ros) in mkn-45 cells and ros scavenger n-acetylcysteine (nac) significantly reversed tcs-induced autophagy. furthermore,nf-κb/p53 pathway was activated during the process of autophagy induced by tcs and the ros generation was mediated by it in mkn-45 cells. in vivo results showed that tcs exerted significantly anti-tumor effect on mkn-45 bearing mice. considering the clinical usage of tcs on other human diseases,these research progresses provided a new insight into cancer research and new therapeutic avenues for patients with gastric cancer. © 2016 the authors