Carvacrol induces apoptosis in human breast cancer cells via Bcl-2/CytC signaling pathway

Abstract Objective To elucidate the molecular mechanisms underlying carvacrol-induced apoptosis in human breast cancer cells. Methods The antiproliferative effect of carvacrol on human breast cancer cell line, HCC1937, was determined using MTT assay, and ultrastructural changes in the treated cells were observed using uranium acetate/lead citrate double staining. Cell cycle analysis was performed using propidium iodide (PI) staining and apoptotic cells were detected using flow cytometric Annexin V-FITC/PI assay. Further, the expression of Bcl-2/CytC signaling pathway-related proteins (Bcl-2, CytC, and Caspase-3) was detected using western blot technique. Results Carvacrol exhibited antiproliferative activity against HCC1937 cells in a concentration-dependent manner, with an IC 50 of 320 mM. Ultrastructure analysis revealed that treatment with carvacrol induced morphologic hallmarks of apoptosis in HCC1937 cells. Carvacrol increased the distribution of HCC1937 cells in the G 0 /G 1 phase and decreased the distribution of HCC1937 cells in the S and G 2 /M phases in a concentration-dependent manner. Moreover, the compound increased the rate of apoptosis and protein expression of Bax, CytC, and Caspase-3 while decreasing the protein levels of Bcl-2 in a dose-dependent manner. Conclusion Carvacrol can inhibit proliferation and induce apoptosis in human breast cancer HCC1937 cells. This effect may be mediated by the activation of the Bcl-2/CytC mitochondrial apoptosis pathway.