College of Life Sciences, China Jiliang University, Hangzhou 310018, China.
College of Science, Technology & Mathematics, Alderson Broaddus University, Philippi, WV 26416, USA.
Molecules. 2020 Mar 30;25(7):1579. doi: 10.3390/molecules25071579.
Among women worldwide, ovarian cancer is one of the most dangerous cancers. Patients undergoing platinum-based chemotherapy might get adverse side effects and develop resistance to drugs. In recent years, natural compounds have aroused growing attention in cancer treatment. Galangin inhibited the growth of two cell lines, A2780/CP70 and OVCAR-3, more strongly than the growth of a normal ovarian cell line, IOSE 364. The IC values of galangin on proliferation of A2780/CP70, OVCAR-3 and IOSE 364 cells were 42.3, 34.5, and 131.3 μM, respectively. Flow cytometry analysis indicated that galangin preferentially induced apoptosis in both ovarian cancer cells with respect to normal ovarian cells. Galangin treatment increased the level of cleaved caspase-3 and -7 via the p53-dependent intrinsic apoptotic pathway by up-regulating Bax protein and via the p53-dependent extrinsic apoptotic pathway by up-regulating DR5 protein. By down-regulating the level of p53 with 20 μM pifithrin-α (PFT-α), the apoptotic rates of OVCAR-3 cells induced by galangin treatment (40 μM) were significantly decreased from 18.2% to 10.2%, indicating that p53 is a key regulatory protein in galangin-induced apoptosis in ovarian cancer cells. Although galangin up-regulated the expression of p21, it had little effect on the cell cycle of the two ovarian cancer cell lines. Furthermore, the levels of phosphorylated Akt and phosphorylated p70S6K were decreased through galangin treatment, suggesting that the Akt/p70S6K pathways might be involved in the apoptosis. Our results suggested that galangin is selective against cancer cells and can be used for the treatment of platinum-resistant ovarian cancers in humans.
在全球女性中，卵巢癌是最危险的癌症之一。接受铂类化疗的患者可能会产生不良反应，并对药物产生耐药性。近年来，天然化合物在癌症治疗中引起了越来越多的关注。高良姜素抑制了两种细胞系 A2780/CP70 和 OVCAR-3 的生长，其抑制作用强于正常卵巢细胞系 IOSE 364。高良姜素对 A2780/CP70、OVCAR-3 和 IOSE 364 细胞增殖的 IC 值分别为 42.3、34.5 和 131.3 μM。流式细胞术分析表明，高良姜素优先诱导两种卵巢癌细胞凋亡，而对正常卵巢细胞影响较小。高良姜素通过上调 Bax 蛋白通过 p53 依赖性内在凋亡途径，以及通过上调 DR5 蛋白通过 p53 依赖性外在凋亡途径，增加 cleaved caspase-3 和 -7 的水平。通过用 20 μM pifithrin-α（PFT-α）下调 p53 水平，用 40 μM 高良姜素处理 OVCAR-3 细胞的凋亡率从 18.2%显著降低至 10.2%，表明 p53 是高良姜素诱导卵巢癌细胞凋亡的关键调节蛋白。尽管高良姜素上调了 p21 的表达，但对两种卵巢癌细胞系的细胞周期影响不大。此外，用高良姜素处理后，磷酸化 Akt 和磷酸化 p70S6K 的水平降低，提示 Akt/p70S6K 途径可能参与凋亡。我们的研究结果表明，高良姜素对癌细胞具有选择性，可用于治疗人类铂耐药性卵巢癌。
