Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Institute of Animal Molecular Biotechnology and Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
Reproduction. 2020 Jun;159(6):745-756. doi: 10.1530/REP-20-0018.
α,β-Thujone is a natural terpenoid found in many medicinal herbs, such as Artemisia absinthium (wormwood), that exhibits antioxidant, anti-diabetic, and anti-tumorigenic effects. α,β-Thujone has numerous functions; it serves as a food ingredient, cosmetic additive, and medicinal remedy. Although the therapeutic properties of α,β-thujone were previously revealed, a comprehensive description of the mechanisms of its anti-cancer potential in choriocarcinoma is yet to be provided. To our knowledge, this study is the first to demonstrate that α,β-thujone attenuates JEG3 and JAR choriocarcinoma cells through a caspase-dependent intrinsic apoptotic pathway. Moreover, α,β-thujone was demonstrated to induce a global mitochondrial defect and ER stress in choriocarcinoma by causing mitochondrial depolarization, calcium overload, and metabolic alterations, thereby leading to energy deprivation, which eventually contributes to the increase in apoptosis of choriocarcinoma cells. Herein, we also revealed the synergistic anti-cancer activity of α,β-thujone via its sensitization effect on paclitaxel in choriocarcinoma cells. Altogether, our findings suggest that α,β-thujone is a novel, natural pharmacological compound that can be used to treat human placental choriocarcinoma.
α,β-侧柏酮是一种天然萜类化合物，存在于许多药用植物中，如青蒿（苦艾），具有抗氧化、抗糖尿病和抗肿瘤作用。α,β-侧柏酮具有许多功能；它可用作食品成分、化妆品添加剂和药物疗法。尽管 α,β-侧柏酮的治疗特性以前已经被揭示，但尚未全面描述其在绒毛膜癌中的抗癌潜力的机制。据我们所知，这项研究首次表明，α,β-侧柏酮通过 caspase 依赖性内在凋亡途径来减弱 JEG3 和 JAR 绒毛膜癌细胞。此外，α,β-侧柏酮通过引起线粒体去极化、钙超载和代谢改变，导致能量剥夺，从而导致绒毛膜癌细胞凋亡增加，证明其在绒毛膜癌中诱导全线粒体缺陷和内质网应激。在此，我们还揭示了 α,β-侧柏酮通过其对绒毛膜癌细胞中紫杉醇的增敏作用而具有协同抗癌活性。总之，我们的研究结果表明，α,β-侧柏酮是一种新型的天然药理学化合物，可用于治疗人类胎盘绒毛膜癌。
