Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
BMC Complement Med Ther. 2020 Mar 20;20(1):94. doi: 10.1186/s12906-020-02890-y.
Ovarian cancer therapy generally involves systemic chemotherapy with anticancer drugs; however, chemotherapy with a platinum-based drug has often been shown to cause adverse reactions and drug resistance in ovarian cancer patients. Evodia rutaecarpa (ER) reportedly shows anticancer activity against various types of cancer cells. However, the effects of ER have not yet been fully uncovered in ovarian cancer.
In the present study, we investigated the anticancer effects of an ER extract and its components against the ovarian cancer cell lines SKOV-33, A2780, RMUG-S and a cisplatin-resistant SKOV-3 cell line (Cis SKOV-3). Cell viability and colony formation assays along with subcellular fractionation analysis, immunoblotting, and immunofluorescence staining were performed.
ER treatment led to a significant reduction in the viability of SKOV-3 cells. Moreover, limonin, a compound found in ER, reduced the viability of both serous-type (SKOV-3 and A2780) and mucinous-type (RMUG-S) ovarian cancer cells by inducing apoptosis via activation of the p53 signaling pathway. Furthermore, limonin reversed the drug resistance through activation of apoptosis in Cis SKOV-3.
Taken together, our findings suggest that limonin contributes to the anti-ovarian cancer effects of ER by inducing apoptosis via activation of the p53 signaling pathway.
卵巢癌的治疗通常涉及使用抗癌药物进行全身化疗;然而,铂类药物化疗常常导致卵巢癌患者出现不良反应和耐药性。吴茱萸(ER)据报道对多种癌细胞具有抗癌活性。然而,ER 在卵巢癌中的作用尚未被充分揭示。
在本研究中,我们研究了 ER 提取物及其成分对卵巢癌细胞系 SKOV-33、A2780、RMUG-S 和顺铂耐药 SKOV-3 细胞系(Cis SKOV-3)的抗癌作用。进行了细胞活力和集落形成测定以及亚细胞分级分析、免疫印迹和免疫荧光染色。
ER 处理导致 SKOV-3 细胞活力显著降低。此外,吴茱萸中的一种化合物 limonin 通过激活 p53 信号通路诱导细胞凋亡,从而降低了浆液型(SKOV-3 和 A2780)和粘液型(RMUG-S)卵巢癌细胞的活力。此外,limonin 通过激活 Cis SKOV-3 中的细胞凋亡来逆转耐药性。
综上所述,我们的研究结果表明,limonin 通过激活 p53 信号通路诱导细胞凋亡,从而有助于 ER 发挥抗卵巢癌作用。