Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA.
Department of Food and Nutrition, Kookmin University, Seoul, 02707, Republic of Korea.
Free Radic Biol Med. 2020 Aug 20;156:26-35. doi: 10.1016/j.freeradbiomed.2020.05.022. Epub 2020 Jun 5.
Phytoestrogens are naturally derived estrogen-like therapeutic compounds that have long been studied for their role as anti-cancer agents and supplements during chemotherapy. Bavachin is a therapeutic phytoestrogen used to treat cancer, inflammation, and diabetes mellitus. Though the therapeutic effects of bavachin on various diseases have been explored, its anti-cancer effects and related mechanisms in human placental choriocarcinoma remain unknown. This is the first study to identify the anti-cancer potential of bavachin on human placental choriocarcinoma cell lines JEG3 and JAR. Placental mitochondria support the elevated energy production required for placental development, through oxidative phosphorylation (OXPHOS). Based on this concept, we hypothesized that mitochondrial targeting by bavachin may contribute to anti-cancer activities in high-OXPHOS subtypes of cancer such as placental choriocarcinoma. Apoptosis and caspase activities were increased by bavachin in placental choriocarcinoma cells. Bavachin altered metabolic phenotypes by regulating electron transport chain complex and OXPHOS to suppress choriocarcinoma cell proliferation. It also led to calcium disruption and endoplasmic reticulum stress accompanied by mitochondrial membrane potential depolarization. It showed synergistic anti-cancer effects with paclitaxel on placental choriocarcinoma cells. Taken together, we suggest that bavachin has therapeutic potential against placental choriocarcinoma and may be used to counter paclitaxel-induced toxicity.
植物雌激素是天然衍生的类雌激素治疗化合物，长期以来一直被研究用作癌症的抗癌剂和化疗补充剂。补骨脂素是一种用于治疗癌症、炎症和糖尿病的治疗性植物雌激素。虽然补骨脂素对各种疾病的治疗作用已经得到了探索，但它在人胎盘绒毛膜癌细胞系 JEG3 和 JAR 中的抗癌作用及其相关机制尚不清楚。这是第一项研究鉴定补骨脂素对人胎盘绒毛膜癌细胞系 JEG3 和 JAR 的抗癌潜力。胎盘线粒体通过氧化磷酸化 (OXPHOS) 为胎盘发育所需的高能量产生提供支持。基于这一概念，我们假设补骨脂素对线粒体的靶向可能有助于高 OXPHOS 亚型癌症（如胎盘绒毛膜癌）的抗癌活性。补骨脂素增加了胎盘绒毛膜癌细胞中的细胞凋亡和半胱天冬酶活性。补骨脂素通过调节电子传递链复合物和 OXPHOS 改变代谢表型，抑制绒毛膜癌细胞增殖。它还导致钙破坏和内质网应激，伴随着线粒体膜电位去极化。它与紫杉醇对胎盘绒毛膜癌细胞表现出协同抗癌作用。综上所述，我们认为补骨脂素对胎盘绒毛膜癌具有治疗潜力，可用于对抗紫杉醇引起的毒性。
