Apomorphine facilitates loss of respiratory chain activity in human epithelial ovarian cancer and inhibits angiogenesis in vivo.,Free Radical Biology and Medicine

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Apomorphine facilitates loss of respiratory chain activity in human epithelial ovarian cancer and inhibits angiogenesis in vivo.
Free Radical Biology and Medicine ( IF 7.1 ) Pub Date : 2020-05-08 , DOI: 10.1016/j.freeradbiomed.2020.05.001
Jin-Young Lee ₁ , Jiyeon Ham ₂ , Whasun Lim ₃ , Gwonhwa Song ₂

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Apomorphine, a therapeutic agent for neurological diseases, is structurally similar to dopamine, and thereby holds potential in cancer therapy. However, there are no reports regarding its anti-cancer effects on human epithelial ovarian cancers (EOCs); therefore, we aimed to elucidate the mechanism underlying its action after drug repositioning. Apomorphine inhibited the proliferation of ES2 and OV90 EOC cells by inducing caspase activation and mitochondrion-associated apoptosis; it also promoted endoplasmic reticulum stress and mitochondrial dysfunction through mitochondrial membrane potential depolarization and mitochondrial calcium overload. Moreover, following apomorphine treatment, we noted the loss of respiratory chain activity by reduction of oxidative phosphorylation and energy-production shift in EOC cells. Further, we verified the anti-angiogenic capacity of apomorphine using fli:eGFP transgenic zebrafish. As a preclinical assessment, we demonstrated the synergistic anti-cancer effects of apomorphine and paclitaxel combination.

中文翻译：

阿扑吗啡在人上皮性卵巢癌中促进呼吸链活性的丧失并在体内抑制血管生成。

阿扑吗啡是神经系统疾病的治疗剂，在结构上与多巴胺相似，因此在癌症治疗中具有潜力。但是，尚无有关其对人类上皮性卵巢癌（EOCs）的抗癌作用的报道。因此，我们旨在阐明药物重新定位后其作用的潜在机制。阿扑吗啡通过诱导caspase激活和线粒体相关的凋亡来抑制ES2和OV90 EOC细胞的增殖。它也通过线粒体膜电位去极化和线粒体钙超载促进内质网应激和线粒体功能障碍。此外，在阿扑吗啡治疗后，我们注意到EOC细胞中的氧化磷酸化减少和能量产生转移导致呼吸链活性降低。进一步，我们使用fli：eGFP转基因斑马鱼验证了阿扑吗啡的抗血管生成能力。作为临床前评估，我们证明了阿扑吗啡和紫杉醇联合治疗具有协同抗癌作用。

更新日期：2020-05-08

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