The therapeutic potential of α,β-
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 α,β-
thujone in ES2 and OV90 human
ovarian cancer cells and its effect on sensitization to
cisplatin. α,β-
thujone inhibited
cancer cell proliferation and induced cell death through
caspase-dependent intrinsic apoptotic pathways. Moreover, α,β-
thujone-mediated endoplasmic reticulum stress was associated with the loss of mitochondrial functions and altered metabolic landscape of
ovarian cancer cells. α,β-
Thujone attenuated blood vessel formation in transgenic zebrafish, implying it has significant antiangiogenic potential. In addition, α,β-
thujone sensitized
ovarian cancer cells to
cisplatin, causing synergistic pharmacological effects. Collectively, our results suggest that α,β-
thujone has therapeutic potential in human
ovarian cancer and functions via regulating multiple intracellular stress-associated metabolic reprogramming and
caspase-dependent apoptotic pathways.