4.7 Article Proceedings Paper

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

Publisher

BLACKWELL PUBLISHING
DOI: 10.1111/j.1749-6632.2009.04722.x

Keywords

P-glycoprotein; wogonin; etoposide; apoptosis; cancer cells

Funding

  1. Takeda Science Foundation

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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.

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