CYCLIC HYDROXAMIC ACID INHIBITORS OF PROSTATE-CANCER CELL-GROWTH - SELECTIVITY AND STRUCTURE-ACTIVITY-RELATIONSHIPS

BACKGROUND. Clinical symptoms of prostatitis, prostatodynia, and benig n prostatic hyperplasia are relieved by the pollen extract cernilton, and the water-soluble fraction of this extract selectively inhibits gr owth of some prostate cancer cells. A cyclic hydroxamic acid, DIBOA, h as been isolated from this extract and mimics its cell growth-inhibito ry properties, but the specificity of DIBOA for inhibition of prostate cell growth has not been reported. METHODS. The in vitro growth inhib itory effects of DIBOA and nine structurally related compounds on DU-1 45 prostate cancer cells, MCF-7 breast cancer cells, and COS-7 monkey kidney cells were determined by treatment of the cells with various co ncentrations of the compounds for 2-6 days. RESULTS. The compounds exh ibited a wide range of potencies, but none of them exhibited selective inhibition of DU-145 cell growth. MCF-7 cells were more sensitive to DIBOA than either DU-145 cells or COS-7 cells. 3,4-dihydroquinoline-2( 1H)-one, compound (4), and 1-hydroxy-6-chloro-3,4-dihydroquinolin-2(1H )-one, compound (7), selectively inhibited MCF-7 cell growth at a conc entration of 10 mu g/ml. 1-hydroxy-3,4-dihydroquinolin-2(1H)-one, comp ound (3), and compound 7 were the most potent inhibitors of DU-145 cel l growth. Treatment of DU-145 cells with 3 (100 mu g/ml) substantially decreased the number of viable cells within 2 days, and no viable cel ls remained in the culture by day 4. CONCLUSIONS. It is unlikely that DIBOA, compound (1), is responsible for the selective growth inhibitio n of prostate cancer cells by the water-soluble fraction of the pollen extract cernilton. Cell morphology results indicate that the growth-i nhibitory effects of DIBOA and structurally related agents on DU-145 c ells are due to their ability to cause cell death. (C) 1998 Wiley-Liss , Inc.