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Activation of NF-kappa B determines the sensitivity of human colon cancer cells to TNF-alpha -induced apoptosis

 Sun-Young Han  ;  Se Young Choung  ;  In-Soon Paik  ;  Hyo-Jin Kang  ;  Youn-Hee Choi  ;  Se Jong Kim  ;  Mi-Ock Lee 
 Biological & Pharmaceutical Bulletin, Vol.23(4) : 420-426, 2000 
Journal Title
Issue Date
Apoptosis/drug effects* ; Apoptosis/genetics ; Base Sequence ; Colonic Neoplasms/metabolism ; Colonic Neoplasms/pathology* ; DNA Primers ; DNA-Binding Proteins/genetics ; Humans ; I-kappa B Proteins* ; Mutation ; NF-KappaB Inhibitor alpha ; NF-kappa B/metabolism* ; Tumor Cells, Cultured ; Tumor Necrosis Factor-alpha/pharmacology*
TNF α ; Colon Cancer ; Apoptosis ; NF-κB
Tumor necrosis factor alpha (TNFalpha) generates a potent cytotoxic effect, however many cancer cells are resistant to TNFalpha-mediated killing and the cause of the differential sensitivity remains to be elucidated. In this study, we demonstrated that TNFalpha induced cell death in four different human colon cancer cell lines. The degree of cytotoxic effect was different in each cell line, in that HCT-15 was relatively sensitive, while DLD-1, HT-29 and WiDr were relatively resistant. TNFalpha induced apoptotic changes such as morphological changes, DNA fragmentation and activation of caspase-3 in HCT-15, but to a lesser degree in the others. Transcriptional expression of TNFR1(p55), as well as that of FLICE, Fas, FADD, DR3, FAF, TRADD, and RIP was similar in these cell lines, indicating that the susceptibility to TNFalpha-induced apoptosis may not be determined by the constitutive expression level of these factors. Interestingly, the cytotoxic effect of TNFalpha was well correlated with the DNA binding activity of NF-kappaB in the colon cancer cell lines. Further, the overexpression of a non-phosphorylated mutant form of IkappaBalpha enhanced the cytotoxicity of TNFalpha in the resistant cell line, DLD-1, indicating that NF-kappaB activity may determine the sensitivity of colon cancer cells to TNFalpha-induced apoptosis. Thus, our results indicate that modulation of NF-kappaB activity may provide a useful tool to sensitize colon cancer cells to TNFalpha treatment.
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1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Se Jong(김세종)
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