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標題: Tazarotene Induces Apoptosis in Human Basal Cell Carcinoma via Activation of Caspase-8/t-Bid and the Reactive Oxygen Species-Dependent Mitochondrial Pathway
作者: Wu, Chieh-Shan
Chen, Gwo-Shing
Lin, Ping-Yi
Pan, I-Hong
Wang, San-Tang
Lin, Sheng Hao
Yu, Hsin-Su
Lin, Chi-Chen
關鍵字: Apoptosis;BH3 Interacting Domain Death Agonist Protein;Carcinoma, Basal Cell;Caspase 3;Caspase 8;Caspase 9;Cell Line, Tumor;Cell Proliferation;Cell Survival;Cytochromes c;Down-Regulation;Enzyme Activation;Fas-Associated Death Domain Protein;G1 Phase Cell Cycle Checkpoints;Humans;In Situ Nick-End Labeling;Inhibitor of Apoptosis Proteins;Keratolytic Agents;Membrane Potential, Mitochondrial;Mitochondria;Nicotinic Acids;Poly(ADP-ribose) Polymerases;Proto-Oncogene Proteins c-bcl-2;RNA Interference;RNA, Small Interfering;Reactive Oxygen Species;Receptors, Death Domain;Signal Transduction;Skin Neoplasms;X-Linked Inhibitor of Apoptosis Protein;bcl-X Protein
Project: DNA and Cell Biology, Volume 33, Issue 10, Page(s) 652-666.
Previous studies suggest that tazarotene, a new member of the acetylenic class of RARβ/γ selective retinoids which is approved to treat a variety of skin diseases, exhibits an anti-proliferative effect in human basal cell carcinoma (BCC) by triggering caspase-dependent apoptosis. However, the detailed molecular mechanisms underlying the anti-tumor activity of tazarotene are poorly understood. This study aims at investigating the molecular mechanisms of tazarotene-induced apoptosis in human BCC cells. Our results are the first to demonstrate that tazarotene induces mitochondria-dependent cleavage of caspase-9 and -3 and PARP in BCC cells by producing reactive oxygen species (ROS) and activating caspase-8 through both ROS and death receptor signaling. These events are accompanied by a decrease in BCL-2 and BCL-xl anti-apoptotic proteins as well as by survivin and XIAP, two IAP family members. Furthermore, our results presented for the first time that tazarotene triggers a convergence of the intrinsic and extrinsic apoptotic pathways via the caspase-8-truncated Bid signaling pathway. Collectively, these data provide insights into the molecular mechanisms underlying tazarotene-induced apoptosis in human BCC cells, suggesting that this compound is a potential anti-skin cancer drug.
ISSN: 1044-5498
DOI: 10.1089/dna.2014.2366
Appears in Collections:生物醫學研究所

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