Inhibition of AIDS-Kaposi's sarcoma cell proliferation following retinoic acid receptor activation

• Published in: Cancer research (Chicago, Ill.) Ill.), 1995-02, Vol.55 (4), p.823-829
• Main Authors: WEI-XING GUO, GILL, P. S, ANTAKLY, T
• Format: Article
• Language: English
• Subjects: Acquired Immunodeficiency Syndrome - complications; Acquired Immunodeficiency Syndrome - drug therapy; Acquired Immunodeficiency Syndrome - pathology; Animals; Antineoplastic agents; Biological and medical sciences; Cell Adhesion - physiology; Cell Division - drug effects; Cell Division - physiology; Cell Nucleus - chemistry; Cell Nucleus - drug effects; Cyclic AMP - biosynthesis; Cyclic AMP - physiology; Drug Synergism; General aspects; Growth Inhibitors - pharmacology; Growth Substances - physiology; Humans; Kinetics; Medical sciences; Mice; Oncostatin M; Peptides - antagonists & inhibitors; Pharmacology. Drug treatments; Rats; Receptors, Retinoic Acid - drug effects; Receptors, Retinoic Acid - physiology; Sarcoma, Kaposi - complications; Sarcoma, Kaposi - drug therapy; Sarcoma, Kaposi - pathology; Tretinoin - pharmacology; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha - antagonists & inhibitors
• ISSN: 0008-5472; 1538-7445

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.