Xanthohumol induces apoptosis via caspase activation, regulation of Bcl-2, and inhibition of PI3K/Akt/mTOR-kinase in human gastric cancer cells.

We assessed the effect of xanthohumol (XN) on gastric cancer (GC) in vitro and in vivo. XN reduced the viability of SGC-7901, SNU216, and SNU668 cells, but not GES-1 non-tumorigenic human gastric epithelial cells. XN induced apoptosis in SGC-7901 cells in a concentration-dependent manner by enhancing the numbers of late and early apoptotic cells. XN also downregulated the anti-apoptotic proteins Bcl-XL and Bcl-2 and upregulated the pro-apoptotic proteins Bax, Bid, PARP, and caspase-3. XN induced phosphorylation of PI3K, Akt, and mTOR in SGC7901 cells. Also, XN reduced the tumour volume and weight by inhibiting the phosphorylation of Akt and mTOR. XN-treated tumours had significantly fewer proliferating cells and more apoptotic cells compared with the control. Our data indicate that XN induces apoptosis of human GC cells in vivo. Thus, XN may have potential as an anti-GC agent.