Inhibition of P-Glycoprotein by Wogonin Is Involved with the Potentiation of Etoposide-Induced Apoptosis in Cancer Cells

Etoposide induces apoptotic cell death in normal and cancer cells. This apoptosis plays a role not only in anticancer effects but also in adverse reactions, such as myelosuppression. Because we had previously found that wogonin, a flavone found in a plant, suppresses thymocyte apoptosis induced by etoposide, we examined the effect of this flavone in cancer cells. Wogonin significantly potentiated etoposide‐induced apoptosis in HL‐60 cells. This flavone impaired the function of P‐glycoprotein and then increased cellular content of etoposide in the cells. Thus, this flavone is likely to act as an inhibitor of P‐glycoprotein and potentiate the apoptotic action of etoposide. On the other hand, wogonin inhibited etoposide‐induced apoptosis in thymocytes, one of the normal cells. The potentiation by wogonin is likely to be a specific action for cancer cells but not normal cells. Therefore, this flavone may be used to reduce the excretion of the anticancer agents via P‐glycoprotein and increase the pharmacological action of it in cancer cells. These results suggest that wogonin may play a role in overcoming multidrug resistance.