Abrogation of G2/M arrest sensitizes curcumin-resistant hepatoma cells to apoptosis

Abstract 

In this study, we showed that curcumin treatment resulted in activation of Chk1-mediated G2 checkpoint, which was associated with the induction of G2/M arrest and the resistance of cancer cells to curcumin-induced apoptosis. Further investigation revealed that inhibition of Chk1 significantly abrogated G2/M arrest and sensitized curcumin-resistant cells to apoptosis via upregulation of Bad and in turn the loss of mitochondrial membrane potential. These results indicate that Chk1-mediated G2/M arrest may serve as a mechanism for curcumin resistance and Chk1 represents a potential target for the reversal of this resistance. Our findings should be helpful for clinical application of curcumin.

Abbreviations: siRNA, short-interfering RNA, RNAi, RNA interference, RT-PCR, reverse transcription-polymerase chain reaction, hPBGD, human porphobilinogen deaminase, FoxM1, forkhead box M1, PI, propidium iodide, p-Chk1, phosphorylated-Ser317-Chk1, p-Chk2, phosphorylated-Thr68-Chk2, p-p38, phosphorylated-Thr180/Tyr182-p38, p-Cdk1, phosphorylated-Tyr15-Cdk1

Keywords: Curcumin, G2/M arrest, Apoptosis, Drug resistance, Hepatoma cells