氧化还原介导的线粒体崩溃驱动ELT3细胞对芹菜素的内在凋亡信号

摘要(中文译文)

子宫平滑肌瘤是妇科最常见的良性肿瘤，也是异常子宫出血、盆腔疼痛和不孕的主要原因。尽管芹菜素（API）具有抗氧化、抗增殖和抗癌活性，但其在子宫平滑肌瘤中的作用机制，尤其是参与氧化应激介导的线粒体凋亡，仍不清楚。本研究探讨了氧化应激在大鼠子宫平滑肌瘤ELT3细胞凋亡中的作用。细胞分别用50和100 µM API 48 h.通过测量活性氧（ROS）、丙二醛（MDA）和谷胱甘肽还原酶（GR）活性来评估氧化应激。还评估了线粒体膜电位（ΔΨm）、细胞增殖、乳酸脱氢酶（LDH）释放以及凋亡相关基因和蛋白质表达。API显著增加ROS和MDA水平，同时降低GR活性，表明氧化应激。这些变化伴随着ΔΨm崩溃、细胞增殖减少、LDH释放增加、p53、Bax、caspase-3和caspase-9上调以及Bcl-2下调，表明内在线粒体凋亡途径的激活。这些发现表明，API通过氧化应激介导的机制诱导内源性线粒体凋亡，为其细胞毒性效应提供了机制证据，并支持其作为治疗子宫平滑肌瘤的植物化学候选物的潜力。

Abstract

Uterine leiomyoma is the most common benign gynecological tumor and a major cause of abnormal uterine bleeding, pelvic pain, and infertility. Although apigenin (API) exhibits antioxidant, antiproliferative, and anticancer activities, its mechanism of action in uterine leiomyoma, particularly the involvement of oxidative stress-mediated mitochondrial apoptosis, remains unclear. This study investigated the role of oxidative stress in API-induced apoptosis using rat uterine leiomyoma ELT3 cells. Cells were treated with 50 and 100 µM API for 48 h. Oxidative stress was assessed by measuring reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione reductase (GR) activity. Mitochondrial membrane potential (ΔΨm), cell proliferation, lactate dehydrogenase (LDH) release, and apoptosis-related gene and protein expression were also evaluated. API significantly increased ROS and MDA levels while decreasing GR activity, indicating oxidative stress. These changes were accompanied by ΔΨm collapse, reduced cell proliferation, increased LDH release, upregulation of p53, Bax, caspase-3, and caspase-9, and downregulation of Bcl-2, indicating activation of the intrinsic mitochondrial apoptotic pathway. These findings demonstrate that API induces intrinsic mitochondrial apoptosis through oxidative stress-mediated mechanisms, providing mechanistic evidence for its cytotoxic effects and supporting its potential as a phytochemical candidate for uterine leiomyoma treatment.

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