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Effects of fenretinide (4‐HPR) on prostate LNCaP cell growth, apoptosis, and prostate‐specific gene expression
Author(s) -
Hsieh TzeChen,
Wu Joseph M.
Publication year - 1997
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/(sici)1097-0045(19971001)33:2<97::aid-pros3>3.0.co;2-j
Subject(s) - fenretinide , lncap , prostate , apoptosis , prostate cancer , medicine , cancer research , gene expression , cell growth , endocrinology , retinoid , gene , biology , cancer , retinoic acid , genetics
BACKGROUND Although fenretinide (4‐HPR) is currently being evaluated in a phase II clinical study for the chemoprevention of prostate cancer [Greenwald et al.: CA 45:31–49, 1995], the mechanism underlying its antineoplastic activity has not been elucidated. METHODS Androgen‐dependent human prostatic LNCaP cells cultured with fetal bovine serum (FBS) were treated with 4‐HPR and evaluated for effects on cell growth and cell cycle phase distribution, induction of apoptosis, and changes in proliferating cell nuclear antigen (PCNA), prostate‐specific antigen (PSA), and androgen receptor (AR) levels. RESULTS LNCaP cells treated with 4‐HPR for 6 days showed 82–95% suppression of cell growth, with accompanying time‐ and dose‐dependent downregulation of PCNA, a partial arrest in G 1 phase of the cell cycle, and a marked increase in the percentage of apoptotic cells. Apoptosis was demonstrated by the characteristic DNA fragmentation pattern seen on agarose gels, and by flow cytometric analysis. 4‐HPR‐induced prostate‐specific phenotype changes included significant downregulated expression of both intracellular and secreted forms of PSA, which were preceded by a reduction of AR expression. CONCLUSIONS These data suggest that 4‐HPR acts as a pleiotropic effector of prostate cell growth and specific gene expression. Prostate 33:97–104, 1997. © 1997 Wiley‐Liss, Inc.