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.