Therapeutic potential of alpha,beta-thujone through metabolic reprogramming and caspase-dependent apoptosis in ovarian cancer cells

Abstract

The therapeutic potential of alpha,beta-thujone, a functional compound found in many medicinal plants of the Cupressaceae, Asteraceae, and Lamiaceae families, has been demonstrated, including in inflammation and cancers. However, its pharmacological functions and mechanisms of action in ovarian cancer remain unclear. We investigated the anticancer properties of alpha,beta-thujone in ES2 and OV90 human ovarian cancer cells and its effect on sensitization to cisplatin. alpha,beta-thujone inhibited cancer cell proliferation and induced cell death through caspase-dependent intrinsic apoptotic pathways. Moreover, alpha,beta-thujone-mediated endoplasmic reticulum stress was associated with the loss of mitochondrial functions and altered metabolic landscape of ovarian cancer cells. alpha,beta-Thujone attenuated blood vessel formation in transgenic zebrafish, implying it has significant antiangiogenic potential. In addition, alpha,beta-thujone sensitized ovarian cancer cells to cisplatin, causing synergistic pharmacological effects. Collectively, our results suggest that alpha,beta-thujone has therapeutic potential in human ovarian cancer and functions via regulating multiple intracellular stress-associated metabolic reprogramming and caspase-dependent apoptotic pathways.