TNF cytotoxicity: effects of HER-2/neu expression and inhibitors of ADP-ribosylation.
Previous studies have implicated ADP-ribosylation in the mechanism of TNF cytotoxicity. In short-term 51Cr-release assays with several mouse and human tumor cell lines, the inhibitors aminobenzamide (ABA) and nicotinamide (NA) of ADP-ribosylation sensitized HER-2/neu-nonoverexpressing cells (CaOV-3 and MCF-7) but not HER-2/neu-overexpressing cells (SKOV-3 and SKBR-3) to TNF. However, both inhibitors alone or in combination with either TNF and/or actinomycin D (AD) caused similar effects on ADP-ribosylation rates of CaOV-3 and SKOV-3 cells after 4 h of treatment. This result suggests that ADP-ribosylation may not be involved in sensitizing these human tumor cells to TNF. Both ABA and NA decreased the TNF sensitivity of L929 cells and either increased or decreased TNF sensitivity of EMT-6 cells in the absence or presence of actinomycin D, respectively. Again, there was no correlation between ADP-ribosylation and TNF cytotoxicity in these mouse cell lines. Thus, modulation of TNF sensitivity by these inhibitors might be linked to a compromised repair mechanism distinct from the effects on ADP-ribosylation alone.
Tang
P
P
Department of Tumor Biology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Hung
M C
MC
Klostergaard
J
J
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D003609:Dactinomycin / Q000494:pharmacology; D015870:Gene Expression; D006801:Humans; D051379:Mice; D009536:Niacinamide / Q000494:pharmacology; D009856:Oncogene Proteins, Viral / Q000235:genetics; D009857:Oncogenes; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D018719:Erb-b2 Receptor Tyrosine Kinases; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000246:Adenosine Diphosphate Ribose; D001549:Benzamides; D003609:Dactinomycin; D009536:Niacinamide; D009856:Oncogene Proteins, Viral; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D018719:Erb-b2 Receptor Tyrosine Kinases; D014409:Tumor Necrosis Factor-alpha; C025160:3-aminobenzamide