DAPK1 modulates a curcumin-induced G2/M arrest and apoptosis by regulating STAT3, NF-κB, and caspase-3 activation

•Curcumin treatment upregulates DAPK1 expression in U251 cells.•The knockdown of DAPK1 attenuates curcumin-induced STAT3 and NF-κB inhibition.•The knockdown of DAPK1 reduces curcumin-induced caspase-3 activation.•The knockdown of DAPK1 inhibits curcumin-induced cell-cycle arrest and apoptosis.•The tumor suppressor DAPK1 is essential for the anti-cancer effects of curcumin.

Curcumin, an active polyphenol extracted from the perennial herb Curcuma longa, controls various molecules involved in tumor cell death. In this study, we found that the tumor suppressor death-associated protein kinase 1 (DAPK1) plays a vital role in the anti-carcinogenic effects of curcumin. We found that curcumin increased DAPK1 expression at the mRNA and protein levels in U251 cells, and that the siRNA-mediated knockdown of DAPK1 attenuated the curcumin-induced inhibition of STAT3 and NF-κB. Moreover, DAPK1 suppression diminished curcumin-induced caspase-3 activation. In addition, we confirmed that DAPK1 was required for a curcumin-induced G2/M cell cycle arrest and apoptosis. Thus, DAPK1 is involved in curcumin-mediated death pathways. Our data suggest novel mechanisms for curcumin in cancer therapy.