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Bavachin suppresses human placental choriocarcinoma cells by targeting electron transport chain complexes and mitochondrial dysfunction.
Free Radical Biology and Medicine ( IF 7.4 ) Pub Date : 2020-06-05 , DOI: 10.1016/j.freeradbiomed.2020.05.022
Jin-Young Lee 1 , Whasun Lim 2 , Gwonhwa Song 3
Affiliation  

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.



中文翻译:

Bavachin通过靶向电子转运链复合物和线粒体功能障碍来抑制人胎盘绒毛膜癌细胞。

植物雌激素是天然来源的类似雌激素的治疗​​性化合物,长期以来一直在研究它们在化疗过程中作为抗癌剂和补充剂的作用。Bavachin是一种治疗性植物雌激素,可用于治疗癌症,炎症和糖尿病。尽管已经探讨了巴伐钦对各种疾病的治疗作用,但其在人胎盘绒毛膜癌中的抗癌作用及其相关机制仍不清楚。这是鉴定巴伐金对人胎盘绒毛膜癌细胞JEG3和JAR的抗癌潜力的第一项研究。胎盘线粒体通过氧化磷酸化(OXPHOS)支持胎盘发育所需的高能量产生。基于这个概念,我们假设巴瓦钦靶向线粒体可能有助于高OXPHOS亚型癌症(如胎盘绒毛膜癌)的抗癌活性。巴瓦钦可增加胎盘绒毛膜癌细胞的凋亡和半胱天冬酶活性。Bavachin通过调节电子转运链复合物和OXPHOS抑制绒癌组织细胞增殖来改变代谢表型。它还导致钙破坏和内质网应激,并伴随线粒体膜电位去极化。它显示了与紫杉醇对胎盘绒毛膜癌细胞的协同抗癌作用。综上所述,我们建议巴瓦钦具有抗胎盘绒毛膜癌的治疗潜力,可用于对抗紫杉醇引起的毒性。巴瓦钦可增加胎盘绒毛膜癌细胞的凋亡和半胱天冬酶活性。Bavachin通过调节电子转运链复合物和OXPHOS抑制绒癌组织细胞增殖来改变代谢表型。它还导致钙破坏和内质网应激,并伴随线粒体膜电位去极化。它显示了与紫杉醇对胎盘绒毛膜癌细胞的协同抗癌作用。综上所述,我们建议巴瓦钦具有抗胎盘绒毛膜癌的治疗潜力,可用于对抗紫杉醇引起的毒性。巴瓦钦可增加胎盘绒毛膜癌细胞的凋亡和半胱天冬酶活性。Bavachin通过调节电子转运链复合物和OXPHOS抑制绒癌组织细胞增殖来改变代谢表型。它还导致钙破坏和内质网应激,并伴随线粒体膜电位去极化。它显示了与紫杉醇对胎盘绒毛膜癌细胞的协同抗癌作用。综上所述,我们建议巴瓦钦具有抗胎盘绒毛膜癌的治疗潜力,可用于对抗紫杉醇引起的毒性。它还导致钙破坏和内质网应激,并伴随线粒体膜电位去极化。它显示了与紫杉醇对胎盘绒毛膜癌细胞的协同抗癌作用。综上所述,我们建议巴瓦钦具有抗胎盘绒毛膜癌的治疗潜力,可用于对抗紫杉醇引起的毒性。它还导致钙破坏和内质网应激,并伴随线粒体膜电位去极化。它显示了与紫杉醇对胎盘绒毛膜癌细胞的协同抗癌作用。综上所述,我们建议巴瓦钦具有抗胎盘绒毛膜癌的治疗潜力,可用于对抗紫杉醇引起的毒性。

更新日期:2020-06-05
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