Germacrone reverses adriamycin resistance in human chronic myelogenous leukemia K562/ADM cells by suppressing MDR1 gene/P-glycoprotein expression

Multidrug resistance (MDR) usually causes chemotherapy failure of chronic myelogenous leukemia (CML). Germacrone is a terpenoid compound and has been reported to reverse MDR in breast cancer cells. However, the effect of germacrone on MDR in CML cells was unknown. The aim of the present study was to evaluate the effect of germacrone on MDR in adriamycin resistance of CML cells. Treatment with a combination of germacrone and adriamycin synergistically inhibited the viability and increased LDH release in K562/ADM cells. Adriamycin induced the apoptosis and caspase-3 activity of K562/ADM cells, and the germacrone treatment significantly enhanced the induction. Adriamycin treatment inhibited the expression of Bcl-2 and induced the expression of Bax, and germacrone enhanced the effect of adriamycin. Germacrone decreased adriamycin-induced expression of MDR1 mRNA and P-gp protein. Overexpression of P-glycoprotein (P-gp) reversed the effect of germacrone on adriamycin resistance in K562/ADM cells. In conclusion, germacrone reversed adriamycin resistance in human chronic myelogenous leukemia K562/ADM cells by suppressing MDR1 gene/P-gp expression. The results indicated that germacrone might be a new MDR reversal agent for CML chemotherapy.