Salicylic acid inhibits ultraviolet- and cis-platinum-induced human immunodeficiency virus expression.
Previous studies have shown that exposure of HeLa cells stably transfected with an HIV-long terminal repeat-chloramphenicol acetyltransferase (HIV-LTR-CAT) construct to many DNA-damaging agents (such as UV light) induces expression from the HIV LTR. By culturing the cells with salicylic acid we demonstrated dose-dependent repression of this UV-or cis-platinum (cis-Pt)-induced HIV expression. While salicylic acid treatment, indomethacin treatment, UV exposure, or cis-Pt treatment alone decreased viability by up to 50%, equal numbers of viable cells were used for the CAT assays. Repression was evident if salicylic acid was administered 2 h before, at the same time as, or up to 6 h after exposure to the DNA-damaging agent. The kinetics were similar for UV- and for cis-Pt-induced HIV expression, and induction was dependent on the UV dose or cis-Pt concentration added to the culture. pH changes of the media alone in the absence of salicylic acid did not affect HIV expression. Indomethacin (100 microM) did not affect UV- or cis-Pt-induced HIV expression. These results suggest a role for the prostaglandins or the cyclo-oxygenase pathway or both in HIV induction mediated by DNA-damaging agents.
Woloschak
G E
GE
Center for Mechanistic Biology and Biotechnology, Argonne National Laboratory, Illinois 60439-4833, USA.
Panozzo
J
J
Schreck
S
S
Libertin
C R
CR
D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D002945:Cisplatin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D015870:Gene Expression / Q000187:drug effects / Q000528:radiation effects; D016325:HIV Long Terminal Repeat / Q000187:drug effects / Q000528:radiation effects; D006367:HeLa Cells; D006801:Humans; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000096:biosynthesis; D012459:Salicylates / Q000494:pharmacology*; D020156:Salicylic Acid; D014162:Transfection; D014466:Ultraviolet Rays
D011994:Recombinant Proteins; D012459:Salicylates; D015500:Chloramphenicol O-Acetyltransferase; D020156:Salicylic Acid; D002945:Cisplatin