Protective effect of plaunotol against doxorubicin-induced renal cell death.

In searching for a safe and effective compound to be used as a chemoprotective agent to prevent toxicity of the anthracyclin doxorubicin to renal cells, the present study demonstrated that plaunotol, a purified acyclic diterpene from Croton stellatopilosus Ohba, showed potential protection against doxorubicin-induced cell death in human proximal tubule cells. Treatment of renal cells with doxorubicin resulted in a significant decrease in viability of the cells, and we next proved that such toxicity was mainly due to apoptotic cell death. Pretreatment of the cells with plaunotol for at least 9 h prior to doxorubicin exposure improved the cells' survival. Plaunotol was shown to up-regulate the anti-apoptotic myeloid cell leukemia-1 (Mcl-1) level whereas it had no effect on the Bcl-2 level. The reduction in Mcl-1 after doxorubicin treatment was shown to be closely associated with the toxic action of the drug, and the increase in Mcl-1 induced by plaunotol pretreatment was able to prevent cell death induced by doxorubicin. Furthermore, the protective effect of plaunotol was evaluated in human lung and melanoma cells. Results indicated that plaunotol had no significantly protective effect in human lung carcinoma cells, whereas it sensitized melanoma cells to drug-induced cell death.