N-(4-hydroxyphenyl) retinamide induces cell cycle specific growth inhibition in PC3 cells.
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 cytotoxicity only at the supraphysiologic concentration of 10.0 microM. However, asynchronously growing cells exposed to 1 microM 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 aphidicolin exhibited significant decreases in DNA synthesis when treated with 1 microM 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 microM 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 microM, and that this inhibition is associated with a suppression of c-myc gene expression.
Igawa
M
M
Department of Surgery, University of Chicago, Illinois.
Tanabe
T
T
Chodak
G W
GW
Rukstalis
D B
DB
D000230:Adenocarcinoma; D000970:Antineoplastic Agents / Q000633:toxicity*; D015152:Blotting, Northern; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000187:drug effects; D017313:Fenretinide / Q000633:toxicity*; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D016259:Genes, myc; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms; D012333:RNA, Messenger / Q000096:biosynthesis; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D012333:RNA, Messenger; D017313:Fenretinide; D013936:Thymidine