N‐(4‐hydroxyphenyl) retinamide induces cell cycle specific growth inhibition in PC3 cells

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Abstract
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 G0/G1 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 G0/G1 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 G1 to S phase at a concentration of 1 μM, and that this inhibition is associated with a suppression of c‐myc gene expression.