Abstract Context: Methyl lucidone (ML) from the dried fruit of Lindera erythrocarpa Makino (Lauraceae) exhibits cytotoxic effects in various cancer cell lines. However, its effects on ovarian cancer cells remain unknown. Objective: This study evaluates the mechanism of ML-induced apoptosis, cell cycle distribution in ovarian cells. Materials and methods: The cytotoxic effect of ML (2.5–80 µM) on OVCAR-8 and SKOV-3 cells was evaluated by MTS assay for 24 and 48 h. Apoptosis and cell cycle arrest were analysed by flow cytometry. PCR, western blot analyses were performed to examine the related signalling pathways. Results: ML induced significant cellular morphological changes and apoptosis in ovarian cancer cells, leading to an antiproliferative effect (IC50 = 33.3–54.7 µM for OVCAR-8 and 48.8-60.7 µM for SKOV-3 cells). Treatment with ML induced cleavage of caspase-3/9 and PARP and release of cytochrome c from the mitochondria. Moreover, ML downregulated the expression of Bcl-2 and Bcl-xL and induced cell cycle arrest in the G2/M phase. Additionally, ML suppressed the expression of cyclin-A/B and promoted that of the cyclin-dependent kinase inhibitors p21 and p27. The expression of death receptors was not altered. Interestingly, ML also inhibited the activity of PI3K/Akt and NF-κB. Discussion and conclusions: ML caused G2/M phase arrest and apoptosis in ovarian cancer cells by activating intrinsic apoptotic pathways and suppressing the PI3K/Akt survival pathway. ML may be a potential anticancer agent to suppress ovarian cancer proliferation; thus, to improve the survival rate of cancer patients.

中文翻译：

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甲基lucidone通过PI3K/Akt/NF-κB通路诱导卵巢癌细胞凋亡和G2/M期阻滞

摘要背景：来自Lindera erythrocarpa Makino (Lauraceae) 干果的甲基lucidone (ML) 在多种癌细胞系中表现出细胞毒性作用。然而，它对卵巢癌细胞的影响仍然未知。目的：本研究评估ML诱导卵巢细胞凋亡的机制、细胞周期分布。材料和方法：ML（2.5-80 µM）对 OVCAR-8 和 SKOV-3 细胞的细胞毒作用通过 MTS 测定进行 24 和 48 小时的评估。通过流式细胞术分析细胞凋亡和细胞周期停滞。进行 PCR、蛋白质印迹分析以检查相关的信号通路。结果：ML 诱导卵巢癌细胞发生显着的细胞形态变化和凋亡，导致抗增殖作用（OVCAR-8 的 IC50 = 33.3-54.7 µM 和 SKOV-3 细胞的 48.8-60.7 µM）。用 ML 处理诱导 caspase-3/9 和 PARP 裂解以及细胞色素 c 从线粒体中释放。此外，ML 下调 Bcl-2 和 Bcl-xL 的表达并在 G2/M 期诱导细胞周期停滞。此外，ML 抑制细胞周期蛋白-A/B 的表达并促进细胞周期蛋白依赖性激酶抑制剂 p21 和 p27 的表达。死亡受体的表达没有改变。有趣的是，ML 还抑制了 PI3K/Akt 和 NF-κB 的活性。讨论与结论：ML通过激活内在凋亡通路和抑制PI3K/Akt存活通路引起卵巢癌细胞G2/M期阻滞和凋亡。ML 可能是抑制卵巢癌增殖的潜在抗癌剂；从而提高癌症患者的生存率。