Ovarian cancer is one of the most serious female malignancies worldwide. Despite intensive efforts being made to overcome ovarian cancer, there still remain limited optional treatments for this disease. Nobiletin, a prospective food-derived phytochemical extracted from citrus fruits, has recently been reported to suppress ovarian cancer cells, but the role of pyroptosis in ovarian carcinoma with nobiletin still remains unknown. In this study, we aim to explore the effect of nobiletin on ovarian carcinoma and further expound the underlying mechanisms of nobiletin-induced ovarian cancer cell death. Our results showed that nobiletin could significantly inhibit cell proliferation, induce DNA damage, and also lead to apoptosis by increasing the cleaved poly (ADP-ribose) polymerase (PARP) level of human ovarian cancer cells (HOCCs) in a dose-dependent manner. Moreover, we revealed that nobiletin decreased mitochondrial membrane potential and induced reactive oxygen species (ROS) generation and autophagy of HOCCs, contributing to gasdermin D-/gasdermin E-mediated pyroptosis. Taken together, nobiletin as a functional food ingredient represents a promising new anti-ovarian cancer candidate that could induce apoptosis and trigger ROS-mediated pyroptosis through regulating autophagy in ovarian cancer cells.

中文翻译：

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Nobiletin通过调节卵巢癌细胞中的自噬来触发活性氧介导的细胞凋亡。

卵巢癌是全世界最严重的女性恶性肿瘤之一。尽管人们为克服卵巢癌付出了巨大的努力，但是对于这种疾病仍然有有限的可选治疗方法。Nobiletin是一种从柑橘类水果中提取的前瞻性食品来源的植物化学物质，最近有报道抑制卵巢癌细胞，但是，使用Nobiletin在卵巢癌中凋亡的作用仍然未知。在这项研究中，我们旨在探讨诺比列汀对卵巢癌的作用，并进一步阐明诺比莱汀诱导的卵巢癌细胞死亡的潜在机制。我们的结果表明，诺比列汀可以显着抑制细胞增殖，诱导DNA损伤，并且还通过以剂量依赖性方式增加人类卵巢癌细胞（HOCC）的裂解多聚（ADP-核糖）聚合酶（PARP）水平而导致凋亡。此外，我们发现，nobiletin降低线粒体膜电位，并诱导HOCC的活性氧（ROS）生成和自噬，从而导致加德明D- /加德明E介导的细胞凋亡。总体而言，诺比列汀作为一种功能性食品成分代表了一种有希望的新型抗卵巢癌候选药物，它可以通过调节卵巢癌细胞的自噬来诱导细胞凋亡并触发ROS介导的细胞凋亡。