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.

中文翻译：

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α,β-thujone 通过代谢重编程和半胱天冬酶依赖性细胞凋亡对卵巢癌细胞的治疗潜力

α,β-thujone 是一种在柏科、菊科和唇形科的许多药用植物中发现的功能性化合物，已被证明具有治疗潜力，包括在炎症和癌症中。然而，其在卵巢癌中的药理作用和作用机制尚不清楚。我们研究了 α,β-thujone 在 ES2 和 OV90 人卵巢癌细胞中的抗癌特性及其对顺铂敏感性的影响。α,β-thujone 通过依赖半胱天冬酶的内在凋亡途径抑制癌细胞增殖并诱导细胞死亡。此外，α,β-thujone 介导的内质网应激与线粒体功能的丧失和卵巢癌细胞代谢格局的改变有关。α,β-Thujone 减弱了转基因斑马鱼的血管形成，这意味着它具有显着的抗血管生成潜力。此外，α,β-thujone 使卵巢癌细胞对顺铂敏感，产生协同药理作用。总的来说，我们的结果表明 α,β-thujone 具有治疗人类卵巢癌的潜力，并通过调节多种细胞内应激相关的代谢重编程和半胱天冬酶依赖性细胞凋亡途径发挥作用。