Enhancement of paclitaxel-induced breast cancer cell death via the glycogen synthase kinase-3β-mediated B-cell lymphoma 2 regulation
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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.
Abstract
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.
참고문헌 (34)
- Embi N, "Glycogen synthase kinase-3 from rabbit skeletal muscle. Separation from cyclic-AMP-dependent protein kinase and phosphorylase kinase", Eur J Biochem, 107, pp.519~527 (1980)
- Jope RS, "The glamour and gloom of glycogen synthase kinase-3", Trends Biochem Sci, 29, pp.95~102 (2004)
- Doble BW, "GSK-3 : tricks of the trade for a multi-tasking kinase", J Cell Sci, 116(Pt 7), pp.1175~1186 (2003)
- Jongyeon Shin, "Swedish mutation within amyloid precursor protein modulates global gene expression towards the pathogenesis of Alzheim5er’s disease", BMB Reports, 43(10), pp.704~709 (2010), 생화학분자생물학회
- Qi Xiong, "Knockdown of endogenous SKIP gene enhanced insulin-induced glycogen synthesis signaling in differentiating C2C12 myoblasts", BMB reports, 42(2), pp.119~124 (2009), 한국생화학분자생물학회
- Beurel E, "The paradoxical pro-and anti-apoptotic actions of GSK3 in the intrinsic and extrinsic apoptosis signaling pathways", Prog Neurobiol, 79, pp.173~189 (2006)
- Hoeflich KP, "Requirement for glycogen synthase kinase-3beta in cell survival and NF-kappaB activation", Nature, 406, pp.86~90 (2000)
- Belkhiri A, "t-Darpp promotes cancer cell survival by up-regulation of Bcl2through Akt-dependent mechanism", Cancer Res, 68, pp.395~403 (2008)
- Tan J, "Pharmacologic modulation of glycogen synthase kinase-3beta promotes p53-dependent apoptosis through a direct Bax-mediated mitochondrial pathway in colorectal cancer cells", Cancer Res, 65, pp.9012~9020 (2005)
- Linseman DA, "Glycogen synthase kinase-3beta phosphorylates Bax and promotes its mitochondrial localization during neuronal apoptosis", J Neurosci, 24, pp.9993~10002 (2004)
- Willis S, "The Bcl-2-regulated apoptotic pathway", J Cell Sci, 116(Pt 20), pp.4053~4056 (2003)
- Kang MH, "Bcl-2 inhibitors: targeting mitochondrial apoptotic pathways in cancer therapy", Clin Cancer Res, 15, pp.1126~1132 (2009)
- Kroemer G, "Mitochondrial control of apoptosis: an overview", Biochem Soc Symp, 66, pp.1~15 (1999)
- Letai A, "Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics", Cancer Cell, 2, pp.183~192 (2002)
- Wang K, "BID : a novel BH3 domain-only death agonist", Genes Dev, 10, pp.2859~2869 (1996)
- Rowinsky EK, "The development and clinical utility of the taxane class of antimicrotubule chemotherapy agents", Annu Rev Med, 48, pp.353~374 (1997)
- Slichenmyer WJ, "Taxol : a new and effective anti-cancer drug", Anticancer Drugs, 2, pp.519~530 (1991)
- Horwitz SB, "Mechanism of action of taxol", Trends Pharmacol Sci, 13, pp.134~136 (1992)
- Schiff PB, "Taxol stabilizes microtubules in mouse fibroblast cells", Proc Natl Acad Sci U S A, 77, pp.1561~1565 (1980)
- Rodi DJ, "Screening of a library of phage-displayed peptides identifies human bcl-2 as a taxol-binding protein", J Mol Biol, 285, pp.197~203 (1999)
- Noh KT, "GSK-3beta-induced ASK1 stabilization is crucial in LPS-induced endotoxin shock", Exp Cell Res, 317, pp.1663~1668 (2011)
- Ciechanover A, "The ubiquitin-proteasome proteolytic pathway", Cell, 79, pp.13~21 (1994)
- Liu X, "Induction of apoptotic program in cell- free extracts: requirement for dATP and cytochrome c", Cell, 86, pp.147~157 (1996)
- Henry-Mowatt J, "Role of mitochondrial membrane permeabilization in apoptosis and cancer", Oncogene, 23, pp.2850~2860 (2004)
- Liu H, "Interleukin 17A inhibits autophagy through activation of PIK3CA to interrupt the GSK3B-mediated degradation of BCL2 in lung epithelial cells", Autophagy, 9, pp.730~742 (2013)
- Noh KT, "Protein kinase C delta(PKCdelta)-extracellular signal-regulated kinase 1", 2(ERK1, J Biol Chem, pp.2012, 287[DOI]
- Kim JW, "Glycogen synthase kinase 3 beta is a natural activator of mitogen-activated protein kinase", extracellular signal-regulated kinase kinase kinase 1(MEKK1), 2003, pp.278, 13995~14001
- Wang Q, "Glycogen synthase kinase-3 is a negative regulator of extracellular signal-regulated kinase", Oncogene, 25, pp.43~50 (2006)
- Yvon AM, "Taxol suppresses dynamics of individual microtubules in living human tumor cells", Mol Biol Cell, 10, pp.947~959 (1999)
- Tange S, "The antineoplastic drug Paclitaxel has immunosuppressive properties that can effectively promote allograft survival in a rat heart transplant model", Transplantation, 73, pp.216~223 (2002)
- Amos LA, "How Taxol stabilises microtubule structure", Chem Biol, 6, pp.R65~R69 (1999)
- Saunders DE, "Paclitaxel-induced apoptosis in MCF-7 breast-cancer cells", Int J Cancer, 70, pp.214~220 (1997)
- Liu K, "Synergistic effect of paclitaxel and epigenetic agent phenethyl isothiocyanate on growth inhibition, cell cycle arrest and apoptosis in breast cancer cells", Cancer Cell Int, 13, pp.10~ (2013)
- 이수정, "The Mycobacterium avium subsp. Paratuberculosis protein MAP1305 modulates dendritic cell-mediated T cell proliferation through Toll-like receptor-4", BMB Reports, 47(2), pp.115~120 (2014), 생화학분자생물학회