Death receptor 5 regulation during selenium-mediated apoptosis in human prostate cancer cells.
Selenium is an essential micronutrient that is currently being tested for prostate cancer chemoprevention. In spite of its significant promise as a chemopreventive agent, the molecular mechanisms of selenium-mediated effects remain to be elucidated. Recent evidence suggests that selenium may mediate its chemopreventive effects by inducing apoptosis in human prostate cancer cells. Here we report that selenium-mediated apoptosis appears to involve membrane death receptor, DR5-dependent pathway in human prostate cancer cells. Selenium specifically upregulated DR5 expression but not that of DR4. Selenium upregulation of DR5 was coupled with caspase 8 activation and Bid cleavage thereby suggesting the existence of a potential cross-talk between the DR5 and the mitochondrial pathways. Thus, our results suggest that DR5 is specifically regulated by selenium and its activation may play an important role in selenium-mediated chemoprevention.
He
Qin
Q
Department of Pharmacology; SUNY Upstate Medical University; Syracuse, New York 13210 USA.
Rashid
Ayesha
A
Rong
Rong
R
Hillman
Michael J
MJ
Huang
Ying
Y
Sheikh
M Saeed
MS
D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D029681:Arabidopsis Proteins; D051023:BH3 Interacting Domain Death Agonist Protein; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D004789:Enzyme Activation; D044943:Fatty Acid Desaturases / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005799:Genes, Dominant; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D012643:Selenium / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation
D000975:Antioxidants; D029681:Arabidopsis Proteins; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D002352:Carrier Proteins; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; C105190:TNFRSF10A protein, human; C505639:TNFRSF10B protein, human; D044943:Fatty Acid Desaturases; C084083:Fad7 protein, Arabidopsis; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D012643:Selenium