Department of Obstetrics and Gynecology, The First Hospital of Jilin University, Xinmin Road 519, Changchun, Jilin, 130001, China.
Institute of Translational Medicine, The First Hospital of Jilin University, Dongminzhu Road 71, Changchun, Jilin, 130001, China.
Med Oncol. 2021 Apr 3;38(5):54. doi: 10.1007/s12032-021-01501-1.
The fatality rate of ovarian cancer ranks first among gynecological tumors, and the prognosis is poor. Diosmetin (Dio), a natural flavonoid obtained from citrus fruits, has been shown to have anti-tumor effects in lung, liver, and skin cancers. We aimed to investigate the effects of Dio on ovarian cancer A2780 and SKOV3 cells along with the underlying mechanisms. Our data showed that Dio inhibited the proliferation, migration, and invasion of these cells and induced their apoptosis. Moreover, Dio upregulated the levels of Bax and cleaved Caspase-3 and PARP while downregulating the level of Bcl2. Mechanistically, our results revealed that Dio inhibited Nrf2 and induced the production of reactive oxygen species (ROS). The ROS scavenger N-acetyl-L-cysteine (NAC) suppressed the inhibitory effect of Dio on the proliferation of the ovarian cancer cells. Additionally, overexpression of Nrf2 partially suppressed the Dio-induced apoptosis and proliferation inhibition in these cells. These findings indicate that Dio exerts an anti-tumor activity by upregulating ROS levels and inhibiting Nrf2, indicating that Dio is a promising chemotherapeutic candidate for the treatment of ovarian cancer.
卵巢癌的死亡率在妇科肿瘤中位居第一，预后较差。地奥司明（Dio）是从柑橘类水果中提取的一种天然黄酮类化合物，已被证明对肺癌、肝癌和皮肤癌具有抗肿瘤作用。我们旨在研究地奥司明对卵巢癌 A2780 和 SKOV3 细胞的影响及其潜在机制。我们的数据表明，地奥司明抑制这些细胞的增殖、迁移和侵袭，并诱导其凋亡。此外，地奥司明上调 Bax 和 cleaved Caspase-3 和 PARP 的水平，同时下调 Bcl2 的水平。在机制上，我们的结果表明，地奥司明抑制 Nrf2 并诱导活性氧（ROS）的产生。ROS 清除剂 N-乙酰-L-半胱氨酸（NAC）抑制了地奥司明对卵巢癌细胞增殖的抑制作用。此外，Nrf2 的过表达部分抑制了地奥司明诱导的这些细胞凋亡和增殖抑制。这些发现表明，地奥司明通过上调 ROS 水平和抑制 Nrf2 发挥抗肿瘤活性，表明地奥司明是治疗卵巢癌的一种有前途的化疗候选药物。
