R-(-)-carvone Attenuated Doxorubicin Induced Cardiotoxicity In Vivo and Potentiated Its Anticancer Toxicity In Vitro

摘要

Background: Doxorubicin is one of the most potent broad-spectrum antitumor and chemotherapeutic agents. However, it produces cardiotoxicity. Aims: To investigate whether R-(-)-carvone exerts a cardioprotective effect against doxorubicin toxicity in vivo and in vitro . Study Design: Cell culture and animal experiment. Methods: The synergistic effect of R-(-)-carvone with doxorubicin was evaluated in the MCF 7 cancer cell line while its protective effect against doxorubicin toxicity was evaluated in the normal heart cell line (H9C2) and in vivo . Furthermore, the mechanism of its cardioprotective effect was studied. Results: R-(-)-carvone exerted cytotoxic action on the MCF 7 cancer cell line with an ICsub50/sub value of 14.22 μM and potentiated the cytotoxic action of doxorubicin, while it decreased the toxicity of doxorubicin on a normal heart cell line. In BALB/c mice, R-(-)-carvone protected the heart from the toxic action of doxorubicin, as was evident by biochemical and histological studies. The protective effect of R-(-)-carvone on the H9C2 heart cell line and on heart in vivo was due to an increase in catalase activity. Conclusion: R-(-)-carvone has synergistic anticancer action with doxorubicin on the MCF 7 cell line while decreasing its cardiotoxicity.