Magnolol Induces Apoptosis And Inhibits Metastasis Via Suppression Of Nf-Kappa B Activation In Human Bladder Cancer.

Abstract Magnolol is a phenolic compound extracted from magnolia officinalis, and known as a common Chinese medicinal material used in the treatment of strokes, colds, etc. Magnolol has also recognized as an anti-inflammation agent which can downregulate several inflammation signals transduction. Several reports suggested that magnolol may also have anti-tumor potential in liver and colon cancer. Nevertheless, the regulatory mechanism of magnolol on apoptosis and NF-κB signaling in human bladder cancer has not been elucidated. Thus, the purpose of the study was to investigate the mechanism and therapeutic efficacy on bladder cancer. First of all, we used MTT assay to investigate the cytotoxicity induction after magnolol treatment in bladder cancer. Then, we used NF-κB translocation assay to evaluate whether the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) was decreased after magnolol treatment. We also detected the apoptosis induction ability of magnolol on extrinsic/intrinsic apoptosis pathway. This study demonstrated that magnolol significantly triggered the accumulation at the sub-G1 phase, the loss of mitochondrial membrane potential, and the activation of cleaved caspase-3, -8 and -9. Further verify the effect of magnolol on the expression of anti-apoptotic related proteins, we performed Western blotting. Magnolol inhibited migration and invasion ability of bladder cancer were investigated by wound healing and invasion assay. Then, we performed Western blotting to detect whether magnolol may inhibit NF-κB-mediated downstream signaling that involving in anti-apoptosis and metastasis such as MCL-1 and MMP9 protein expression. Moreover, the reduction of Cyclin D1 protein expression was used to evaluate the inhibition of cell proliferation by magnolol. In sum, our result demonstrated that magnolol induced extrinsic and intrinsic apoptosis mechanism and inhibit invasion/migration ability of bladder cancer was associated with the inactivation of NF-κB. Citation Format: Sin-Rong Lee, Zhao-Lin Tan, Yuan Chang, I-Tsang Chiang, Fei-Ting Hsu. Magnolol induces apoptosis and inhibits metastasis via suppression of NF-κB activation in human bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 978.