Xanthohumol inhibits non-small cell lung cancer via directly targeting T-lymphokine-activated killer cell-originated protein kinase.

Xanthohumol is a principal prenylated chalcone isolated from hops. Previous studies have shown that xanthohumol was effective against various types of cancer, but the mechanisms, especially the direct targets for xanthohumol to exert an anticancer effect, remain elusive. Overexpression of T-lymphokine-activated killer cell-originated protein kinase (TOPK) promotes tumorigenesis, invasion and metastasis, implying the likely potential for targeting TOPK in cancer prevention and treatment. In the present study, we found that xanthohumol significantly inhibited the cell proliferation, migration and invasion of non-small cell lung cancer (NSCLC) in vitro and suppressed tumor growth in vivo, which is well correlated with inactivating TOPK, evidenced by reduced phosphorylation of TOPK and its downstream signaling histone H3 and Akt, and decreased its kinase activity. Moreover, molecular docking and biomolecular interaction analysis showed that xanthohumol was able to directly bind to the TOPK protein, suggesting that TOPK inactivation by xanthohumol is attributed to its ability to directly interact with TOPK. The findings of the present study identified TOPK as a direct target for xanthohumol to exert its anticancer activity, revealing novel insight into the mechanisms underlying the anticancer activity of xanthohumol.