Berbamine Suppresses the Progression of Bladder Cancer by Modulating the ROS/NF‐ κ B Axis

作者：Chenglin Han, Zilong Wang, Shuxiao Chen, Lin Li, Yingkun Xu, Weiting Kang, Chunxiao Wei, Hongbin Ma, Muwen Wang, Xunbo Jin · 发表于：Oxidative Medicine and Cellular Longevity · 年份：2021 · DOI：10.1155/2021/8851763 · 被引用次数：37 · 研究领域：Berberine and alkaloids research、Ginger and Zingiberaceae research、Aldose Reductase and Taurine

Berbamine (BBM), one of the bioactive ingredients extracted from Berberis plants, has attracted intensive attention because of its significant antitumor activity against various malignancies. However, the exact role and potential molecular mechanism of berbamine in bladder cancer (BCa) remain unclear. In the present study, our results showed that berbamine inhibited cell viability, colony formation, and proliferation. Additionally, berbamine induced cell cycle arrest at S phase by a synergistic mechanism involving stimulation of P21 and P27 protein expression as well as downregulation of CyclinD, CyclinA2, and CDK2 protein expression. In addition to suppressing epithelial‐mesenchymal transition (EMT), berbamine rearranged the cytoskeleton to inhibit cell metastasis. Mechanistically, the expression of P65, P‐P65, and P‐I κ B α was decreased upon berbamine treatment, yet P65 overexpression abrogated the effects of berbamine on the proliferative and metastatic potential of BCa cells, which indicated that berbamine attenuated the malignant biological activities of BCa cells by inhibiting the NF‐ κ B pathway. More importantly, berbamine increased the intracellular reactive oxygen species (ROS) level through the downregulation of antioxidative genes such as Nrf2, HO‐1, SOD2, and GPX‐1. Following ROS accumulation, the intrinsic apoptotic pathway was triggered by an increase in the ratio of Bax/Bcl‐2. Furthermore, berbamine‐mediated ROS accumulation negatively regulated the NF‐ κ B p...