Anticancer activity of Voacangine against human oral cancer cells is due to G2M cell cycle arrest, ROS-mediated cell death and inhibition of PI3KAKT signalling pathway.
Oral cancer is the 6th most prevalent type of cancer and is responsible for high human morbidity and mortality. The present study was designed to investigate the anticancer effects of Voacangine against human oral cancer and to decipher the underlying molecular mechanisms responsible for its anticancer properties. CCC-1 oral cancer cell line and normal hTRET-OME cell line were used in this study. Cell viability was determined by MTT assay. Acridine orange (AO) ethidium bromide (EB) and annexin Vpropidium iodide (PI) assay were used for assessment of apoptosis. Cell cycle analysis and reactive oxygen species (ROS) determination was done by flow cytometry. The protein expression was determined by western blot analysis. The results showed that Voacangine caused a remarkable decline in proliferation of SCC-1 human oral cancer cells with negligible toxic effects on the normal human hTRET-OME cells. The IC50 of Voacangine was 9 µM against SCC-1 cells relative to IC50 of 100 µM against normal hTRET-OME cells. The reduction of the proliferative rates was attributed to the induction of ROS triggered apoptosis which was associated with activation of Caspase-3, upregulation of Bax and suppression of Bcl-2. Voacangine induced G2M cell cycle arrest in a dose-dependent manner. Additionally, the anticancer effects of Voacangine on oral cancer cells were exerted through the inhibition of PI3KAKT signaling cascade. Taken all together, we conclude that Voacangine is a potent anticancer molecule and may be utilized for the development of systemic therapy for oral cancer.