TY - JOUR ID - 89036 TI - Bishonokiol A Induces Multiple Cell Death in Human Breast Cancer MCF-7 Cells JO - Asian Pacific Journal of Cancer Prevention JA - APJCP LA - en SN - 1513-7368 AU - Li, Hong-Mei AU - Li, Bohan AU - Ma, Hui AU - Sun, Xiaolong AU - Zhu, Meilin AU - Dai, Yiqun AU - Ma, Tao AU - Huo, Qiang AU - Wu, Cheng-Zhu AD - School of Pharmacy, Bengbu Medical University, 2600 Donghai Road, Bengbu, Anhui, China. AD - Department of Medicinal Chemistry, School of Pharmacy, Bengbu Medical University, 2600 Donghai Road, Bengbu, Anhui, China. Y1 - 2020 PY - 2020 VL - 21 IS - 4 SP - 1073 EP - 1080 KW - breast cancer KW - bishonokiol A KW - cell death KW - Necroptosis KW - cyclophilin D DO - 10.31557/APJCP.2020.21.4.1073 N2 - Objective: A dimeric neolignan, bishonokiol A (BHNKA) isolated from Magnolia grandiflora, significantly inhibits the proliferation of human breast cancer cells. However, the exact mechanism of BHNKA induced breast cancer cell death is unknown. In this study, we investigated the pharmacological mechanism underlying BHNKA induced MCF-7 cell death. Methods: Cell viability measurement was performed by the MTT assay. Flow cytometry with PI staining, DAPI staining, and electron microscopy were used to analyze cellular death modes. In addition, western blotting, siRNA transfection, ATP assay, and fluorescence microscopy were used to determine the mechanism of BHNKA induced MCF-7 cell death. Results: BHNKA induced cell death by apoptosis, necroptosis and autophagy at the same concentration and time in MCF-7 cells, and electron microscopy confirmed these results. The mechanism of BHNKA triggered apoptosis and autophagy in MCF-7 cells was primarily due to an increase in the Bax/Bcl-2 ratio and simultaneous up-regulation of LC3-II protein expression, respectively. BHNKA induced necroptosis by activation of the RIP1-RIP3-MLKL necroptosis cascade, up-regulation of cyclophilin D (CypD) protein expression to stimulate ROS generation. We further demonstrated that siRNA-mediated down-regulation of CypD protected against BHNKA induced cell death. Conclusions: These results suggest that BHNKA may be a potential lead compound for development as an anti-breast cancer agent for induction of multiple cell death pathways. UR - https://journal.waocp.org/article_89036.html L1 - https://journal.waocp.org/article_89036_92006d6fef96da761860ab449d01c837.pdf ER -