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Cyclic hydroxamic acid inhibitors of prostate cancer cell growth: Selectivity and structure activity relationships

✍ Scribed by Roberts, Kenneth P.; Iyer, Ramaswamy A.; Prasad, Girija; Liu, Lee T.; Lind, Robert E.; Hanna, Patrick E.


Publisher
John Wiley and Sons
Year
1998
Tongue
English
Weight
520 KB
Volume
34
Category
Article
ISSN
0270-4137

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✦ Synopsis


Background:

Clinical symptoms of prostatitis, prostatodynia, and benign prostatic hyperplasia are relieved by the pollen extract cernilton, and the water-soluble fraction of this extract selectively inhibits growth of some prostate cancer cells. a cyclic hydroxamic acid, diboa, has been isolated from this extract and mimics its cell growth-inhibitory properties, but the specificity of diboa for inhibition of prostate cell growth has not been reported.

Methods:

The in vitro growth inhibitory effects of diboa and nine structurally related compounds on du-145 prostate cancer cells, mcf-7 breast cancer cells, and cos-7 monkey kidney cells were determined by treatment of the cells with various concentrations of the compounds for 2-6 days.

Results:

The compounds exhibited 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 concentration of 10 micrograms/ml. 1-hydroxy-3,4-dihydroquinolin-2(1h)-one, compound (3), and compound 7 were the most potent inhibitors of du-145 cell growth. treatment of du-145 cells with 3 (100 micrograms/ml) substantially decreased the number of viable cells within 2 days, and no viable cells remained in the culture by day 4.

Conclusions:

It is unlikely that diboa, compound (1), is responsible for the selective growth inhibition of prostate cancer cells by the water-soluble fraction of the pollen extract cernilton. cell morphology results indicate that the growth-inhibitory effects of diboa and structurally related agents on du-145 cells are due to their ability to cause cell death.


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