Anticancer activity of isomultiflorenol against human cervical cancer cells due to G2/M cell cycle arrest, autophagy and mitochondrial mediated apoptosis

Abstract

Purpose: To determine the anticancer effect of a pentacyclic triterpenoid, isomultiflorenol, against human cervical cancer.Methods: The proliferation of cancer cells was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyl tetrazolium bromide (MTT) assay. Cell viability was measured with colony forming assay, while flow cytometry was used to study phase distribution in cancer cell mitosis. Electron microscopy was employed for the determination of autophagy induction in the cancer cells, while western blotting was used to assay protein expressions.Results: Isomultiflorenol significantly (p < 0.05) inhibited the proliferation and viability of cervical cancer cells in a concentration-dependent manner. The IC50 of isomultiflorenol was 10 μM for HeLa cells, and 90 μM for normal EV304 cells. The anti-proliferative effects were exerted as a result of arrest of HeLa cells at G2/M phase. The G2/M phase cells increased from 10.34 % in control to 30.21 % on treatment with 20 μM isomultiflorenol. Furthermore, administration of isomultiflorenol led to induction of cancer cell autophagy via mitochondrial apoptotic signaling.Conclusion: Isomultiflorenol inhibits human cervical cancer cells in vitro by inducing cell cycle arrest and autophagy. Thus, it is a potential lead molecule in the development of cervical cancer chemotherapy. Keywords: Cervical cancer, Terpenoids, Isomultiflorenol, Autophagy, Cell cycle arrest, Apoptosis