Document 0676
 DOCN  M9550676
 TI    Inhibition of AIDS-Kaposi's sarcoma cell proliferation following
       retinoic acid receptor activation.
 DT    9505
 AU    Guo WX; Gill PS; Antakly T; Department of Pathology, University of
       Montreal, Quebec, Canada.
 SO    Cancer Res. 1995 Feb 15;55(4):823-9. Unique Identifier : AIDSLINE
       MED/95153673
 AB    Retinoids, a group of natural and synthetic vitamin A analogues the
       receptors of which belong to the superfamily of steroid receptors, can
       exert profound effects on growth and/or differentiation of embryonic and
       neoplastic cells. Kaposi's sarcoma (KS), previously a rare multicentric
       neoplasm, has become epidemic with HIV infection, although the etiology
       of KS remains obscure. In the present study, the effects of two potent
       retinoids, all-trans-retinoic acid (RA) and 13-cis-RA, on the expression
       of retinoic acid receptor alpha and the growth of AIDS-related KS
       (AIDS-KS) cells were examined. The proliferation of AIDS-KS cells was
       significantly inhibited by RA and 13-cis-RA in a dose-dependent manner
       with 50% inhibitory concentration of 1.4 x 10(-10) M and 4.7 x 10(-9) M,
       respectively, which correlate with their potency. Growth inhibition was
       time dependent with maximal inhibition of 90% after 3 days of treatment
       with 10(-8) M RA. Growth inhibition by RA was further potentiated by
       forskolin (1 microM), an intracellular cyclic AMP-inducing agent.
       Moreover, RA treatment blocked the proliferative effect of oncostatin M
       and tumor necrosis factor alpha, two major KS autocrine growth factors.
       The effects of RA were accompanied by a dramatic increase in nuclear
       staining for retinoic acid receptor alpha and in the relative number of
       strongly positive retinoic acid receptor alpha nuclei. Finally, RA
       induced morphological changes as KS cells became more flattened, better
       spread, and more adhesive to the substrate. These results suggest that
       retinoids inhibit proliferation of AIDS-KS cells and further support
       their utility as therapeutic agents in AIDS-KS.
 DE    Acquired Immunodeficiency Syndrome/COMPLICATIONS/*DRUG THERAPY/
       *PATHOLOGY  Animal  Cell Adhesion/PHYSIOLOGY  Cell Division/DRUG
       EFFECTS/PHYSIOLOGY  Cell Nucleus/CHEMISTRY/DRUG EFFECTS  Cyclic
       AMP/BIOSYNTHESIS/PHYSIOLOGY  Drug Synergism  Growth
       Inhibitors/PHARMACOLOGY  Growth Substances/PHYSIOLOGY  Human  Kinetics
       Mice  Peptides/ANTAGONISTS & INHIB  Rats  Receptors, Retinoic Acid/*DRUG
       EFFECTS/*PHYSIOLOGY  Sarcoma, Kaposi's/COMPLICATIONS/*DRUG
       THERAPY/*PATHOLOGY  Support, Non-U.S. Gov't  Tretinoin/*PHARMACOLOGY
       Tumor Cells, Cultured  Tumor Necrosis Factor/ANTAGONISTS & INHIB
       JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
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