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Bioorg Med Chem ; 18(16): 6197-207, 2010 Aug 15.
Article in English | MEDLINE | ID: mdl-20637639

ABSTRACT

Photodynamic therapy (PDT) employing exogenous photosensitizers is currently being approved for treatment of basal cell carcinoma (BCC). 2-(4-Aminophenyl)benzothiazoles (6) consist of chromophoric structure and absorb light in the UVA (315-400 nm). These results encouraged us to design and synthesize a diversity of 2-phenylbenzothiazoles (6). Studies on the apoptotic mechanism involved in photosensitive effects induced by UVA-activated 6 in BCC cells are carried out in the present article. 6-UVA-treated cells displayed several features of apoptosis, including an increase in the sub-G1 population, a significantly increased annexin V binding, and activation of caspase-3. 6-UVA induced a decrease in mitochondrial membrane potential (Deltapsi(mt)) and ATP via enhanced ROS generation and promoted phosphorylation of extracellular signal-regulated kinase (ERK) and p38 MAPK expression. These results suggest that 6-UVA elicits photosensitive effects in mitochondria processes which involve ERK and p38 activation, and ultimately lead to BCC cell apoptosis.


Subject(s)
Benzothiazoles/chemistry , Benzothiazoles/pharmacology , Carcinoma, Basal Cell/drug therapy , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Apoptosis/drug effects , Apoptosis/radiation effects , Benzothiazoles/chemical synthesis , Cell Line, Tumor , Cell Survival/drug effects , Cell Survival/radiation effects , Humans , MAP Kinase Signaling System/drug effects , Mitochondria/drug effects , Mitochondria/pathology , Mitochondria/radiation effects , Photochemotherapy , Photosensitizing Agents/chemical synthesis , Ultraviolet Rays
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