Peking University Third Hospital, Research Center of Clinical Epidemiology, Beijing 100191, P.R. China.
Peking University Third Hospital, Department of Tumor Chemotherapy and Radiation Sickness, Beijing 100191, P.R. China.
Oncol Rep. 2020 Sep;44(3):1266-1274. doi: 10.3892/or.2020.7654. Epub 2020 Jun 22.
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, G1 phase cell cycle arrest, autophagy, and intracellular reactive oxygen species (ROS) generation in MDA‑MB‑231 cells. The number of APE1‑/γH2AX‑/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.
近年来，乳腺癌治疗的新进展显著提高了患者的生存率；然而，复发仍是一个主要问题。目前的治疗方法对乳腺癌的系统治疗并非治愈性的。天然产物可能被用于治疗癌症。最近，泽泻作为一种常用的传统中药，其具有广泛的药理活性。然而，其化合物作用于乳腺癌的机制尚不清楚。本研究旨在探讨泽泻天然治疗剂治疗乳腺癌的潜力。用人乳腺癌 MDA-MB-231 细胞分别用泽泻中的四种主要原甾烷三萜类化合物，包括泽泻醇 A、泽泻醇 A-24-乙酸酯、泽泻醇 B 和泽泻醇 B-23-乙酸酯进行处理。其中，泽泻醇 A 显著抑制细胞活力。泽泻醇 A 诱导 MDA-MB-231 细胞凋亡、G1 期细胞周期停滞、自噬和细胞内活性氧（ROS）生成。与阴性对照细胞相比，APE1-/γH2AX-/LC3-II 阳性细胞的数量也明显更高。所有这些结果都是剂量依赖性的。用泽泻醇 A 处理后，cleaved caspase-3、cleaved caspase 9、Bcl-2 和 p-p38 的表达表明细胞凋亡。cyclin A 和 cyclin D1 表达的变化与泽泻醇 A 处理时的细胞周期停滞有关。此外，用泽泻醇 A 处理时 LC3-II 的表达表明自噬。泽泻醇 A 通过诱导 ROS 和 DNA 损伤，在人乳腺癌细胞中诱导自噬依赖性细胞凋亡。因此，泽泻醇 A 可能成为治疗乳腺癌的一种新的治疗剂。
