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N‐(4‐hydroxyphenyl) retinamide induces cell cycle specific growth inhibition in PC3 cells
Author(s) -
Igawa Mikio,
Tanabe Tetsuyuki,
Chodak Gerald W.,
Rukstalis Daniel B.
Publication year - 1994
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/pros.2990240605
Subject(s) - aphidicolin , cell cycle , cell growth , cell culture , microbiology and biotechnology , biology , growth inhibition , retinoic acid , cancer research , cell , chemistry , biochemistry , genetics
The synthetic retinoid N‐(4‐hydroxyphenyl) retinamide (4‐HPR) has been demonstrated to inhibit the development of primary and metastatic neoplasms in several animal models. In order to investigate the effect of 4‐HPR on human prostate adenocarcinoma, we designed a series of in vitro experiments with the PC3 cell line to evaluate effects on proliferation, cell cycle kinetics, and c‐myc mRNA expression. 4‐HPR demonstrated cytoxicity only at the supraphysiologic concentration of 10.0 μM. However, asynchronously growing cells exposed to 1 μM 4‐HPR demonstrated a 51% reduction in proliferation rate, associated with an accumulation of cells in the G 0 /G 1 phase of the cell cycle. PC3 cells synchronized with serum deprivation or aphidicoline exhibited significant decreases in DNA synthesis when treated with 1 μM 4‐HPR. Additionally, these cells were found to accumulate in G 0 /G 1 and S phase. Northern blots indicated a significant decrease in c‐myc mRNA expression in asynchronously growing cells with continuous administration of 1 μM 4‐HPR for 6 days. These data suggest that 4‐HPR can inhibit growth of PC3 cells as a consequence of a block in cell cycle transition from G 1 to S phase at a concentration of 1 μM, and that this inhibition is associated with a suppression of c‐myc gene expression. © 1994 Wiley‐Liss, Inc.