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A selective retinoid with high activity against an androgen‐resistant prostate cancer cell type
Author(s) -
Lu XianPing,
Fanjul Andrea,
Picard Nathalie,
Shroot Braham,
Pfahl Magnus
Publication year - 1999
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19990118)80:2<272::aid-ijc17>3.0.co;2-x
Subject(s) - retinoid , cancer research , retinoid x receptor , biology , prostate cancer , retinoic acid , cell growth , endocrinology , nuclear receptor , androgen receptor , medicine , cancer , cell culture , biochemistry , genetics , transcription factor , gene
Retinoic acid (RA) and its natural and synthetic analogs, the retinoids, regulate many biological processes, including development, differentiation, cell growth, morphogenesis, metabolism and homeostasis. Retinoid effects are mediated by specific nuclear receptors, the RARs and RXRs. Because of their ability to control cell growth and induce differentiation, retinoids are being examined for the prevention and treatment of several cancers. The majority of retinoids so far analyzed and available inhibit primarily cell proliferation and tumor progression but cannot eliminate cancer cells. In addition, the beneficial effects of the natural retinoids are undermined by undesirable side effects, possibly due to indiscriminate activation of all retinoid receptor subtypes and response pathways. Here, we show that a synthetic retinoid, CD‐271, that activates selectively the RARγ subtype in a given context, shows increased anti‐proliferative activity against certain carcinoma cells over all‐ trans ‐retinoic acid (tRA). CD‐271 exhibits enhanced activity against DU‐145 prostate adenocarcinoma cells through apoptosis‐inducing activity, while tRA does not. The selective anti‐cancer cell action appears to be receptor‐mediated as an RAR antagonist reverses the inhibition. This profile was not seen with other selective retinoids, such as RARα–selective agonists, anti‐AP‐1 compounds and a non‐apoptosis inducing RARγ agonist. Our data point to a specific role for RARγ in controlling the growth of the prostate, consistent with previous RARγ gene knockout data. The identified retinoid represents a new class of compounds with potential for the treatment of prostate cancer. Int. J. Cancer80:272–278, 1999. © 1999 Wiley‐Liss, Inc.