Screening and identification of cell death and mitophagy-inducing phytochemicals from Bacopa monnieri extract against oral cancer cells

Abstract

Bacopa monnieri is a traditional herbal medicine well known for its antioxidant, anti-inflammatory, and neuroprotective effect. Hyperactivation of inflammasome sustains cancer progression by promoting cell proliferation, metastasis, epithelial-mesenchymal transition, and angiogenesis. Oral carcinogens such as arecoline promote NLRP3 inflammasome activation via mitochondrial dysfunction, which in turn promotes cancer progression. Hence, mitophagy-mediated removal of dysfunctional mitochondria maintains the mitochondrial pool and renders NLRP3 inflammasome activation. In this study, we have identified the anticancer and anti-inflammatory effect of ethanolic extract from Bacopa monnieri against Cal33 and FaDu cells which was further fractioned into ethyl acetate and aqueous fractions. Anticancer studies with Cal33 and FaDu indicate that the aqueous fraction of the ethanolic extract (BM-AF) is more potent than others. Interestingly, BM-AF inhibited clonogenic potential and cell migration and induced apoptosis in oral cancer. In addition, BM-AF induces mitophagy and mitochondrial fission in Cal33 cells, and it showed that BM-AF-induced mitophagy was abrogated in the presence of mitochondrial fission inhibitor Mdivi1and autophagy inhibitors. Furthermore, BM-AF inhibits arecoline-induced NLRP3 inflammasome activation in Cal33 cells. In conclusion, Bacopa monnieri fraction BM-AF has potent anticancer activity through apoptosis and mitophagy-dependent inhibition of NLRP3 inflammasome activation in oral cancer cells.