Abstract
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.