机构：[1]Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210024, Jiangsu, China江苏省人民医院[2]Department of Otorhinolaryngology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210024, Jiangsu, China外科系统耳鼻咽喉科江苏省人民医院[3]Department of Dermatology, The First Affiliated Hospital of Kunming Medical University, Yunnan Provincial Institute of Dermatology, Kunming 650032, Yunnan, China内科科室皮肤科昆明医科大学附属第一医院[4]Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China江苏省人民医院[5]Department of Dermatology, BenQ Medical Center, Nanjing Medical University, Nanjing 210019, Jiangsu, China
The aim of the current study is to investigate the effect of ceramides on genistein-induced anti-melanoma effects in vitro. We found that exogenously added cell-permeable short-chain ceramides (C6) dramatically enhanced genistein-induced growth inhibition and apoptosis in cultured melanoma cells. Genistein treatment only induced a moderate intracellular ceramides accumulation in B16 melanoma cells. Two different agents including 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP), a ceramide glucosylation inhibitor, and the sphingosine kinase-1 (SphK1) inhibitor II (SKI-II), a sphingosine (ceramides precursor) phosphorylation inhibitor, both facilitated genistein-induced ceramides accumulation and melanoma cell apoptosis. Co-administration of ceramide (C6) and genistein induced a significant Akt inhibition and c-jun-NH2-kinase (JNK) activation, caspase-3 cleavage and cytochrome c release. Caspase-3 inhibitor z-DVED-fmk, JNK inhibitor SP 600125, or to restore Akt activation by introducing a constitutively active form of Akt (CA-Akt) diminished ceramide (C6) and genistein co-administration-induced in vitro anti-melanoma effect. Our study suggests that increasing cellular level of ceramides may sensitize genistein-induced anti-melanoma effects. (C) 2012 Elsevier Inc. All rights reserved.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [810701297, 81101188]; Postdoctoral Science Foundation of ChinaChina Postdoctoral Science Foundation [20100470649]
第一作者机构：[1]Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210024, Jiangsu, China
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推荐引用方式(GB/T 7714)：
Ji Chao,Yang Yan-li,He Li,et al.Increasing ceramides sensitizes genistein-induced melanoma cell apoptosis and growth inhibition[J].BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS.2012,421(3):462-467.doi:10.1016/j.bbrc.2012.04.012.
APA：
Ji, Chao,Yang, Yan-li,He, Li,Gu, Bing,Xia, Ji-ping...&Bi, Zhi-gang.(2012).Increasing ceramides sensitizes genistein-induced melanoma cell apoptosis and growth inhibition.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,421,(3)
MLA：
Ji, Chao,et al."Increasing ceramides sensitizes genistein-induced melanoma cell apoptosis and growth inhibition".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 421..3(2012):462-467
