Brevilin A induces apoptosis and autophagy of colon adenocarcinoma cell CT26 via mitochondrial pathway and PI3K/AKT/mTOR inactivation.
Brevilin A is a sesquiterpene lactone isolated from Centipeda minima and possesses inhibitory effects on proliferation of various tumor cells. In this study, Brevilin A inhibitory effect on proliferation and its molecular mechanism of action were investigated both in vivo and in vitro in colon adenocarcinoma CT26 cells. The results indicated that the inhibitory effect of Brevilin A in CT26 proliferation was dose-dependent and this effect was due to apoptosis. Furthermore, Brevilin A increased ROS levels, decreased mitochondrial membrane potential (MMP) and induced apoptosis of CT26 cell in a dose-dependent manner. Apoptosis induced by Brevilin A was higher than that induced by adriamycin under the same dose. Cleaved-caspase-8, cleaved-caspase-9 and cleaved-caspase-3 were up-regulated after Brevilin A treatment, together with an increase of Bax protein expression, while Bcl-2 was reduced. Further investigation revealed that Brevilin A inhibited the phosphorylation of PI3K, AKT and mTOR and promoted the expressions of autophagy-related proteins LC3-II, Beclin1 and Atg5 and consequent formation of autophagosomes, whereas 3-methyladenine (3-MA), a type III PI3K inhibitor, inhibited autophagosomes formation induced by Brevilin A. In vivo investigation suggested that Brevilin A significantly inhibited the growth of CT26 tumor compared to adriamycin and concurrently promoted the expressions of LC3-II and cleaved-caspase-3 in tumor tissues. Our results demonstrated that the anti-tumor activity of Brevilin A was mainly achieved by the induction of cell apoptosis and autophagy, suggesting a promising potential as antitumor drug against colon adenocarcinoma.
['You|Pengtao|P|', 'Wu|Hezhen|H|', 'Deng|Meng|M|', 'Peng|Jingling|J|', 'Li|Fangping|F|', 'Yang|Yanfang|Y|']
D000072283:A549 Cells D000230:Adenocarcinoma D000818:Animals D000970:Antineoplastic Agents D017209:Apoptosis D001343:Autophagy D020169:Caspases D045744:Cell Line, Tumor D049109:Cell Proliferation D003110:Colonic Neoplasms D003437:Crotonates D006367:HeLa Cells D056945:Hep G2 Cells D006801:Humans D008297:Male D053078:Membrane Potential, Mitochondrial D051379:Mice D008807:Mice, Inbred BALB C D008928:Mitochondria D019869:Phosphatidylinositol 3-Kinases D051057:Proto-Oncogene Proteins c-akt D012717:Sesquiterpenes D015398:Signal Transduction D058570:TOR Serine-Threonine Kinases
Brevilin A Apoptosis Autophagy CT26 Mechanism