Nitric oxide induces apoptosis in cutaneous T cell lymphoma (HuT-78) by downregulating constitutive NF-kappaB.
Constitutive active NF-kappaB have been shown to protect cutaneous T cell lymphoma (CTCL) cells from apoptosis. In the present study, we have studied the cytotoxic potential of nitric oxide generating compound, sodium nitroprusside (SNP) on CTCL cell line, HuT-78. Treatment of cells with SNP resulted in decrease in mitochondrial membrane potential, cytochrome c release, activation of caspase-3 and poly (ADP ribose) polymerase cleavage. SNP treatment inhibited activation of NF-kappaB in a concentration dependent manner. SNP increased the expression of IkappaBalpha without affecting the phosphorylation of IkappaBalpha. Downregulation of NF-kappaB by SNP decreased p65 nuclear translocation as evident by confocal fluorescence microscopy. Further it was found that SNP treatment caused downregulation of Bcl-2 family member (Bcl-xl) in HuT-78 cells. Thus, we have provided evidence that SNP induces apoptosis in CTCL cell line, HuT-78 by downregulating constitutive NF-kappaB and thereby Bcl-xl expression.
Rishi
Loveena
L
Division of Cell Biology and Immunology, Institute of Microbial Technology, Chandigarh-160 036, India.
Dhiman
Rohan
R
Raje
Manoj
M
Majumdar
Sekhar
S
D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000032:analysis / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D016410:Lymphoma, T-Cell, Cutaneous; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009573:Nitrites / Q000032:analysis; D009599:Nitroprusside / Q000494:pharmacology; D051996:Transcription Factor RelA / Q000378:metabolism
D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D020030:Nitric Oxide Donors; D009573:Nitrites; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha; D009599:Nitroprusside; D009569:Nitric Oxide; D045304:Cytochromes c; D053148:Caspase 3