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Highlights: [•] 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. [ABSTRACT FROM AUTHOR]

Parthenolide (PTL) is a sesquiterpene lactone isolated from feverfew and exhibits potent antitumor activity against various cancers. Many studies indicate that PTL treatment leads to apoptosis, however, the mechanism has not been defined. Here, we observed that cells underwent autophagy shortly after PTL treatment. Inhibition of autophagy by knocking out autophagy associated gene atg 5 blocked PTL-induced apoptosis. Surprisingly, PTL decreased the level of translation initiation factor eIF4E binding protein 1 (4E-BP1) in correlation with autophagy. Ectopic expression or shRNA knockdown of 4E-BP1 further verified the effect of 4E-BP1 on PTL-induced autophagy. Meanwhile, PTL elevated the cellular reactive oxygen species (ROS) which located upstream of the depletion of 4E-BP1, and contributed to the consequent autophagy. This study revealed 4E-BP1 as a trigger for PTL-induced autophagy and may lead to therapeutic strategy to enhance the efficacy of anticancer drugs. [ABSTRACT FROM AUTHOR]