Ovatodiolide exerts anticancer effects on human cervical cancer cells via mitotic catastrophe, apoptosis and inhibition of NF-kB pathway.

PURPOSE: Being the second most prevalent cancer in females, cervical cancer causes significant mortality across the globe. Owing to the adverse effects and inefficiency of the currently used anticancer drugs, there are increasing efforts for the identification of safer and effective anticancer agents from plants. This study was undertaken to investigate the anticancer effects of Ovatodiolide, a plant-derived macrocyclic diterpenoid, against the human cervical cancer. METHODS: The anticancer effects were examined by WST-1 proliferation assay. DAPI and annexin V/propidium iodide (PI) staining were used for apoptosis detection. Flow cytometry was used for cell cycle analysis. Protein expression was used for cell cycle analysis. RESULTS: The results revealed that Ovatodiolide caused inhibition of the viability of all the cervical cancer cells with IC50 ranging from to 14 to 56 µM. Ovatodiolide exerted more profound antiproliferative effects on the DoTc2 cells with and IC50 of 14 µM. However, minimal cytotoxicity was observed for the normal cervical cells as evidenced from the IC50 of 100 µM. Ovatodiolide triggered apoptotic cell death of the DoTc2 cells. The induction of apoptosis was accompanied with increase in Bax and decrease in Bcl-2 expression. Ovatodiolide also caused arrest of the DoTc2 cells at the G2/M phase of the cell cycle, which was also accompanied with suppression of cyclin B1 expression. Investigation of the effects of Ovatodiolide on NF-kB expression revealed that the molecule caused significant decrease in the expression of the NF-kB expression. CONCLUSION: Taken together, Ovatodiolide may prove a lead molecule for the development of systemic therapy for cervical cancer.