Topoisomerase poisons activate the transcription factor NF-kappaB in ACH-2 and CEM cells.
The nuclear factor kappaB (NF-kappaB) is involved in T cell activation and enhances HIV-1 gene expression. It is activated in response to numerous stimuli, including oxidative stress. Oxidative stress damages membrane lipids, proteins and nucleic acids. We have shown previously that oxidative DNA damage generated by photosensitization could trigger activation of NF-kappaB. We now show that a series of topoisomerase poisons (actinomycin D, camptothecin, daunomycin and etoposide) also activate NF-kappaB (NFKB1/RelA dimer) in ACH-2 and CEM cells. This activation is inhibited by pyrrolidine dithiocarbamate. In ACH-2 cells latently infected by HIV-1, camptothecin, daunomycin and etoposide are able to enhance virus production. Since topoisomerase poisons cause the formation of single- and double-strand breaks in DNA, these lesions might be capable of triggering NF-kappaB activation. Indeed, DNA damaging agents generating adducts (trans-platin and 4-nitroquinoline 1-oxide) and/or crosslinks in DNA (cisplatin and mitomycin C) do not or only weakly activate NF-kappaB in T cell lines.
Piret
B
B
Laboratory of Fundamental Virology, Institute of Pathology, University of Liège, Belgium.
Piette
J
J
D000975:Antioxidants / Q000494:pharmacology; D002166:Camptothecin / Q000494:pharmacology; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D003609:Dactinomycin / Q000494:pharmacology; D003630:Daunorubicin / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism*; D019384:Nucleic Acid Synthesis Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D059004:Topoisomerase I Inhibitors; D015533:Transcriptional Activation / Q000187:drug effects; D014775:Virus Activation / Q000187:drug effects / Q000502:physiology
D000975:Antioxidants; D016328:NF-kappa B; D019384:Nucleic Acid Synthesis Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D059004:Topoisomerase I Inhibitors; D003609:Dactinomycin; D005047:Etoposide; D004247:DNA; D003513:Cycloheximide; D004264:DNA Topoisomerases, Type I; D002166:Camptothecin; D003630:Daunorubicin