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

Abstract

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.

• Authors: K P Roberts, R A Iyer, G Prasad, L T Liu, R E Lind, P E Hanna
• Journal: The Prostate (Prostate) Vol. 34 Issue 2 Pg. 92-9 (Feb 01 1998) ISSN: 0270-4137 [Print] United States
• PMID: 9465940 (Publication Type: Journal Article)

Chemical References

• Benzoxazines
• Oxazines
• 2,4-dihydroxy-1,4-benzoxazin-3-one

Topics

• Benzoxazines
• Breast Neoplasms (pathology)
• Cell Division (drug effects, physiology)
• Cell Line
• Dose-Response Relationship, Drug
• Female
• Humans
• Kidney (cytology)
• Male
• Oxazines (chemistry, pharmacology)
• Prostatic Neoplasms (pathology)
• Structure-Activity Relationship
• Time Factors
• Tumor Cells, Cultured