Pulegone induced apoptotic and anti-proliferative potential in cervical cancer via P53, BAX and BCL2

Cervical cancer is ranked the fourth most ocervical cancerurring gynecologic malignancy and thus becomes a serious point of concern in the world of cancer. The morbidity and mortality of cervical cancer is still high despite advancements in its prevention and treatment. The anticancer effects of pulegone in conjunction with conventional chemotherapy provide a better therapeutic approach. The present study was designed to assess the implications of putative in vitro anti-proliferative effects of pulegone against cervical cancer. HeLa, VERO, CaSKi and SiHa cells were cultured in complete DMEM media. MTT assay was performed to evaluate cell viability. p53 and annexin V was evaluated through ELISA for apoptosis. Immunocytochemistry was performed to determine cell death. Total protein content was determined by using Western blotting. The cytotoxicity of HeLa cells was dramatically increased with pulegone at a dose of 10 µM with no cytotoxic effect on VERO cells at all doses. Pulegone-treated HeLa cells showed an increasing degree of Annexin V staining. After pulegone treatment, fluorescent Hoechst 33,342 staining showed that nuclei were fragmented and condensed, a typical apoptotic morphology. Immunocytochemistry of P53 showed an increased apoptosis in Pulegone-treated cells compared to control and Cisplatin. Protein expression of BAX was increased and BCL2 decreased in pulegone treated cells. The present study portrayed that pulegone has potential anti-proliferative activities against cervical cancer cell lines with no toxic effect on normal cells. Thus, pulegone can be used as a potent therapeutic option either alone or when co-administered with traditional chemotherapy in the treatment of cervical cancer.