Se-methylselenocysteine activates caspase-3 in mouse mammary epithelial tumor cells in vitro.
Se-methylselenocysteine (MSC) inhibits mouse mammary epithelial tumor cell (TM6) growth. When synchronized TM6 cells were exposed to 50 microM MSC, either for 30 minutes or continuous, the 116 kDa poly(ADP-ribose)polymerase (PARP) was cleaved to an 85 kDa fragment indicative of cells undergoing apoptosis. The earliest cleaved PARP appears at 24 hr time point followed by elevated levels of 85 kDa fragment at 34 hr and 48 hr time points when the cells were exposed to continuous treatment with MSC. Results also showed that MSC increased caspase-3 activity at 24 hr time point. In addition, continuous treatment with MSC induced DNA fragmentation at 34 hr and 48 hr time points with caspase-3 gene expression moderately increased at 16 hr and 24 hr time points. Caspase-6 and -8 were also involved in the MSC-induced apoptosis but to a lesser extent. These results suggest that MSC mediates cleavage of PARP and apoptosis by activating one or more caspases in synchronized TM6 cells and the events are dependent on the duration of treatment.
Unni
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Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Singh
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Ganther
H E
HE
Sinha
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D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D003545:Cysteine / Q000031:analogs & derivatives / Q000494:pharmacology*; D053938:DNA Fragmentation; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004789:Enzyme Activation; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000473:pathology*; D051379:Mice; D016566:Organoselenium Compounds / Q000494:pharmacology*; D017279:Selenocysteine / Q000031:analogs & derivatives; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured
D016588:Anticarcinogenic Agents; D004273:DNA, Neoplasm; D016566:Organoselenium Compounds; D017279:Selenocysteine; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D003545:Cysteine; C002979:selenomethylselenocysteine; D013936:Thymidine