Bigelovin is a selective retinoid X receptor α agonist. Bigelovin suppresses tumor growth through inducing apoptosis and autophagy via the inhibition of mTOR pathway regulated by ROS generation.It is also known as a potent cytotoxic sesquiterpene lactone from Inula sp.

BigV exhibited potential anti-tumor activities against human liver cancer in vitro and in vivo.?BigV reduced the cell proliferation and colony formation.?BigV induced apoptosis through improving the cleavage of Caspase-3 and poly (ADP-ribose) polymerase 1 (PARP-1).?The process was along with the activation of autophagy, as proved by the enhanced accumulation of autophagosomes, the microtubule-associated light chain 3B-II (LC3B-II) and Beclin-1, and p62 decrease.?Further, the autophagy blockage markedly sensitized BigV-induced cell death, indicating the cytoprotective function of autophagy in liver cancer cell lines.?In addition, BigV treatment inactivated the pathway of protein kinase B (AKT)/mammalian target of rapamycin (mTOR)/ribosomal protein S6 kinase (p70S6K).?Of note, BigV-induced cell death was abolished by over-expressing the phosphorylation of mTOR.?Intriguingly, the induction of apoptosis and autophagy were eliminated by the pretreatment of reactive oxygen species (ROS) scavenger N-acetyl-l-cysteine (NAC), suggesting that ROS played an important role in the regulation of BigV-induced cell death.

In vivo studies demonstrated that BigV significantly suppressed the growth of HepG2 cancer xenograft tumors through the activation of apoptosis and autophagy in a dose-dependent manner with low systemic toxicity.?Revealed that BigV had significant antitumor effects against human liver cancer and it may potentially be used as a novel antitumor agent for the prevention of liver cancer.