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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
Enzyme Activation
Fas-Associated Death Domain Protein
G1 Phase Cell Cycle Checkpoints
In Situ Nick-End Labeling
Inhibitor of Apoptosis Proteins
Keratolytic Agents
Membrane Potential, Mitochondrial
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
摘要: 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
Appears in Collections:生物醫學研究所



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