Xanthohumol inhibits non-small cell lung cancer by activating PUMA-mediated apoptosis

Deregulation of apoptosis signaling is an important feature of cancer cells and plays an essential role in tumorigenesis. Xanthohumol is an active ingredient in Traditional Chinese Medicines Hops (Humulus lupulus L.). Recently studies have shown the profound anti-tumor activities of Xanthohumol in multiple cancer models. However, its potency in non-small cell lung cancer (NSCLC) and the underlying mechanisms are still elusive. Here, we have investigated the potency of Xanthohumol against NSCLC cells in vitro and xenograft mouse models. Xanthohumol suppressed cell viability, colony formation and induced apoptosis in A549, H520, and H358 cells. Xanthohumol activated mitochondrial apoptosis through upregulation of (p53-upregulated modulator of apoptosis) PUMA expression. After Xanthohumol treatment, the Akt activity was inhibited, which resulted in dephosphorylation of FOXO3a and PUMA induction. Silent PUMA or FOXO3a impaired Xanthohumol-induced apoptosis in NSCLC cells. In nude mice, Xanthohumol administration suppressed NSCLC xenograft tumor growth and increased PUMA expression in tumor tissues. Briefly, our studies revealed a novel mechanism by which Xanthohumol exerted its anti-tumor activity in a PUMA-dependent manner in NSCLC cells.