Unlocking the potential of beta sitosterol: Augmenting the suppression of oral cancer cells through extrinsic and intrinsic signalling mechanisms

Saudi Dent J. 2023 Dec;35(8):1007-1013. doi: 10.1016/j.sdentj.2023.08.003. Epub 2023 Aug 14.

Abstract

The global increase in the prevalence of oral neoplasms and related deaths can be attributed to social development and lifestyle factors, leading to poor prognosis and a lack of early clinical detection. Oral cancer ranks ranked sixth mostly diagnosed cancer and is a leading cause of cancer-related deaths. In light of these circumstances, our objective was to assess the potential of β-sitosterol, a naturally occurring herbal compound, as an anticancer agent against KB cells, a representative cell line for oral cancer. Our study primarily focused on evaluating the cytotoxic effect and mRNA expression of apoptotic proteins by β-sitosterol on KB cells. The results demonstrated a remarkable cytotoxic effect, leading to cell death. Further investigation using flow cytometric analysis revealed that this cell death was mediated through the initiation of the apoptotic signalling by β-sitosterol. The use of the bioinformatic tool, STITCH, supported our study by predicting drug-protein interactions and suggesting that β-sitosterol may play a significant role in targeting apoptotic pathways. Additionally, docking results were employed to validate the findings demonstrating high binding affinity of β-sitosterol with apoptotic-mediated signalling targets. To gain deeper insights into the molecular insights, we measured mRNA levels for BAX, BCL-2, MCL-1, P53, P21, MDM2, caspase3, and caspase9. Based on our comprehensive findings, our study concludes that β-sitosterol holds significant therapeutic potential against oral cancer cells. These results strongly suggest that this herbal compound should be further explored as a potential treatment option for oral cancer for clinical trial.

Keywords: Apoptosis; Drug-protein interactions; Gene expression; KB-cells; Oral neoplasms; β-sitosterol.