Alisol A is potentially therapeutic in human breast cancer cells
Alisol A is potentially therapeutic in human breast cancer cells
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泽泻醇 A 对人类乳腺癌细胞具有潜在治疗作用
DOI：
10.3892/or.2020.7654
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发表时间：
2020-09-01
期刊：
影响因子：
4.2
通讯作者：
Zhao, Hongmei
中科院分区：
文献类型：
--
作者：
Shi, Yanyan;Wang, Mopei;Zhao, Hongmei
乳腺癌治疗的最新进展显著提高了患者的生存率；然而，复发仍然是一个主要问题。用现有疗法对乳腺癌进行全身治疗是无法治愈的。天然产物有可能用于治疗癌症。近年来，作为一种流行的中药，泽泻具有广泛的药理活性。然而，其化合物对乳腺癌起作用的机制尚不清楚。本研究旨在探讨泽泻天然药物治疗乳腺癌的潜力。用泽泻A、泽泻A 24-醋酸酯、泽泻B和泽泻B 23-醋酸酯四种主要的原烷三萜处理人乳腺癌MDA-MB-231细胞。其中，alisol A显著抑制细胞活力。Alisol A诱导MDA-MB-231细胞凋亡、G(1)期细胞周期阻滞、自噬和细胞内活性氧（ROS）的产生。与阴性对照细胞相比，APE1-/ γ H2AX-/LC3-II阳性细胞的数量也显著增加。所有这些结果都是剂量依赖性的。Cleaved caspase-3、Cleaved caspase 9、Bcl-2和p-p38的表达表明alisol A处理后细胞凋亡。细胞周期蛋白A和细胞周期蛋白D1的表达变化与alisol A处理后细胞周期阻滞有关。此外，LC3-II在alisol A处理后的表达表明自噬。艾利索A可通过诱导活性氧和DNA损伤诱导人乳腺癌细胞自噬依赖性凋亡。因此，艾利索A可能成为一种新的乳腺癌治疗剂。
Recent developments in breast cancer therapy have significantly improved patient survival rate; however, recurrence remains a major problem. Systemic treatment of breast cancer with available therapies is not curative. Natural products can be potentially used for treating cancer. Recently, a wide range of pharmacological activities has been reported for Alismatis Rhizoma, a popular traditional Chinese medicine. However, the mechanisms via which its compounds act on breast cancer remain unclear. The present study aimed to investigate the potential of natural therapeutic agents from Alismatis Rhizoma for treating breast cancer. Human breast cancer MDA-MB-231 cells were treated with four main protostane triterpenes from Alismatis Rhizoma, including alisol A, alisol A 24-acetate, alisol B and alisol B 23-acetate. Among these, alisol A significantly inhibited cell viability. Alisol A induced cell apoptosis, G(1)phase cell cycle arrest, autophagy, and intracellular reactive oxygen species (ROS) generation in MDA-MB-231 cells. The number of APE1-/gamma H2AX-/LC3-II positive cells was also significantly higher compared with that of negative control cells. All these results were dose-dependent. Cleaved caspase-3, cleaved caspase 9, Bcl-2, and p-p38 expression indicated cell apoptosis after alisol A treatment. The changes in cyclin A and cyclin D1 expression was associated with cell cycle arrest upon alisol A treatment. Furthermore, LC3-II expression upon alisol A treatment was indicative of autophagy. Alisol A treatment can induce autophagy-dependent apoptosis in human breast cancer cells via induction of ROS and DNA damage. Thus, Alisol A might serve as a new therapeutic agent against breast cancer.