Subscribe to RSS
DOI: 10.1055/s-0032-1307587
Tumor Suppressive Activity of Evodiamine in Breast Cancer Cells Via Inhibition of Ras/MEK/ERK Pathway and Activation of PPARγ
Evodiamine (Evo, 1), a major constituent of the Chinese herb Evodiae fructus, is known to suppress the growth of cancer cells; however, its underlying molecular mechanisms have not been fully elucidated. The present study was designed to evaluate and elucidate the anticancer effect and mechanism of Evo on breast cancer cells. We found that Evo induced potent growth inhibition on MCF-7, T47D, MDA-MB-231 and MDA-MB-468 breast cancer cells in a time- and dose-dependent manner. Flow cytometry showed that Evo suppressed breast cancer cells growth by cell cycle arrest at the G2/M phase, which was accompanied with an increase of the expression of cyclin B1, p-Rb, and a decrease of the expression of p-cdc2 and p21. Evo was found to increase sub-G1 accumulation, nuclear morphologic changes and annexin-V positive staining, indicating apoptotic induction. Meanwhile, Evo activated caspases 7, 9 and the cleavage of PARP. More importantly, we report for the first time that Evo was able to increase PPARγ activity and down-regulate the expression of Ras, p-MEK1/2, p-ERK in breast cancer cells. The increase in PPARγ activity was partially diminished in the presence of PPARγ specific inhibitor T0070907, indicating that Evo may act as a ligand of PPARγ. Our data suggest that Evo can be considered to be a PPARγ agonist and thus a promising candidate for a chemotherapeutic agent against breast cancer.
Acknowledgements: This study was supported by the Research Fund of the University of Macau (MYRG 208 (Y1-L4)-ICMS11-WYT).