ACTIVATION OF PHORBOL DIESTER-INDUCED HUMAN IMMUNODEFICIENCY VIRUS GENE EXPRESSION IS INHIBITED BY ET-18-OCH3 AND RELATED ETHER LIPID ANALOGS (MEETING ABSTRACT)

Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.

ACTIVATION OF PHORBOL DIESTER-INDUCED HUMAN IMMUNODEFICIENCY VIRUS GENE EXPRESSION IS INHIBITED BY ET-18-OCH3 AND RELATED ETHER LIPID ANALOGS (MEETING ABSTRACT)

Proc Annu Meet Am Assoc Cancer Res; 33:A2487 1992. Unique Identifier : AIDSLINE ICDB/92685008
Daniel LW; Civoli F; Smitherman PK; Wake Forest Univ., Winston-Salem, NC 27157-1016

Abstract: The phorbol diester tumor promoter (TPA) stimulates protein kinase C (PKC), mimics the effects of growth factors on cell proliferation and stimulates replication of latent human immunodeficiency virus (HIV). Activation of the transcription factor NF-kB is associated with these effects. ET-18-OCH3 (1-O-octadecyl-2-O-methyl-rac-glycero-3 phosphocholine) inhibits PKC and its biological effects may be due to inhibition of PKC and subsequent inhibition of NF-kB activation. To test the effects of ET-18-OCH3 on NF-kB expression, we have used a cell line, 293.27.2, transfected with a plasmid containing the HIV-long terminal repeat linked to the lacZ gene. Treatment of these cells with either TPA or tumor necrosis factor (TNF) caused a marked stimulation of NF-kB activation. ET-18-OCH3 inhibited HIV gene expression in response to TPA. However, ET-18-OCH3 did not inhibit TNF-induced activation which does not appear to require PKC. These data indicate that ET-18-OCH3 inhibition of HIV gene expression is signal specific and not due to nonspecific toxicity. Analogs of ET-18-OCH3 including He-PC, BM 41.440 and SRI 62,834 also inhibit TPA-induced HIV gene expression. Therefore, PKC inhibition and the inhibition of TPA-induced gene expression may be important in the mechanism of action of ether-linked lipids as inhibitors of cell proliferation and HIV replication.

Keywords: beta-Galactosidase/GENETICS/METABOLISM Antineoplastic Agents/*PHARMACOLOGY Cell Line Cloning, Molecular Gene Expression Regulation, Viral/*DRUG EFFECTS Human HIV/DRUG EFFECTS/*GENETICS HIV Long Terminal Repeat/*DRUG EFFECTS NF-kappa B/METABOLISM Phospholipid Ethers/*PHARMACOLOGY Tetradecanoylphorbol Acetate/PHARMACOLOGY Transfection ABSTRACT
920830
M9281091

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