ReferenceID 4657
Berbamine Suppresses the Progression of Bladder Cancer by Modulating the ROS/NF- κ B Axis
Oxid Med Cell Longev
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
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- Reference Id
- 4657
- Evidence Id
- 21247
- Core Evidence Id
- 21247
- Source Reference Id
- 2578
- Herb2 Reference Id
- HBREF003375
- Subject Paper Key
- HBIN017888_33520087
- Pubmed Id
- 33520087
- Doi
- 10.1155/2021/8851763
- Paper Title
- Berbamine Suppresses the Progression of Bladder Cancer by Modulating the ROS/NF- κ B Axis
- Paper Abstract
- 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-IkappaBalpha 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-kappaB 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-kappaB pathway to a certain degree. Consistent with our in vitro results, berbamine successfully inhibited tumor growth and blocked the NF-kappaB pathway in our xenograft model. To summarize, our data demonstrated that berbamine exerts antitumor effects via the ROS/NF-kappaB signaling axis in bladder cancer, which provides a basis for further comprehensive study and presents a potential candidate for clinical treatment strategies against bladder cancer.
- Journal
- Oxid Med Cell Longev
- Publish Year
- 2021
- Experiment Subject
- Experiment Type
- Cell Experiment
- Phenotype Related
- Tumor; Malignancies; Bca; Bladder Cancer
- Paper Title Cn
- Paper Title En
- Berbamine Suppresses the Progression of Bladder Cancer by Modulating the ROS/NF- κ B Axis
- Bilingual Status
- semi_complete