Enhancement of paclitaxel-induced breast cancer cell death via the glycogen synthase kinase-3β-mediated B-cell lymphoma 2 regulation

BMB Reports

Gil Sun Cha^2¹  Kyung Tae Noh^1²  In Duk Jung^2³  Tae Heung Kang^2⁴  Kwang-Youn Kim^4⁵  Joon Cho^3⁶ 

[1] Department of Immunology, KU Open Innovation Center, College of Medicine, Konkuk University, Chungju 27478^2;Department of Infectious Diseases, Armed Forces Medical Research Institute, Daejeon 34059^1;Department of Microbiology and Immunology, Pusan National University School of Medicine, Yangsan 50612^5;Department of Neurosurgery, Konkuk University Hospital, Seoul 05030^3;National Research Laboratory of Molecular Virology, Department of Pathology, School of Medicine, The Catholic University of Korea, Seoul 03083, Korea^6;School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan 44919^4

关键词: B-cell lymphoma 2;   

DOI  :  

学科分类：生物化学/生物物理

来源: Korean Society for Biochemistry and Molecular Biology

【 摘 要 】

Glycogen synthase kinase-3β (GSK-3β) is a serine/threonine protein kinase that is known to mediate cancer cell death. Here, we show that B-cell lymphoma 2 (Bcl-2), an anti-apoptotic protein, is regulated by GSK-3β and that GSK-3β-mediated regulation of Bcl-2 is crucial for mitochondrial-dependent cell death in paclitaxel-stimulated cells. We demonstrate that MCF7 GSK- 3β siRNA cells are more sensitive to cell death than MCF7 GFP control cells and that in the absence of GSK-3β, Bcl-2 levels are reduced, a result enhanced by paclitaxel. Paclitaxel-induced JNK (c-Jun N-terminal kinase) activation is critical for Bcl-2 modulation. In the absence of GSK-3β, Bcl-2 was unstable in an ubiquitination-dependent manner in both basal- and paclitaxeltreated cells. Furthermore, we demonstrate that GSK-3β-mediated regulation of Bcl-2 influences cytochrome C release and mitochondrial membrane potential. Taken together, our data suggest that GSK-3β-dependent regulation of Bcl-2 is crucial for mitochondria-dependent cell death in paclitaxel-mediated breast cancer therapy.

【 授权许可】

Unknown