Activity of D-glucarate analogues: synergistic antiproliferative effects with retinoid in cultured human mammary tumor cells appear to specifically require the D-glucarate structure.
D-Glucarate has shown modest chemopreventive and synergistic chemopreventive effects with retinoids in a number of tumor models as well as a similar antiproliferative effect in MCF-7 human tumor cells in culture. It has been postulated that D-glucarate exerts some of its effects by equilibrium conversion to D-glucarolactone, a potent beta-glucuronidase inhibitor. In the present study, D-glucarate and a number of its analogues, including D-glucarolactone, were evaluated as antiproliferatives in the MCF-7 model with and without added retinoid. Results suggest that the effects of glucarate are reasonably specific for its structure and may not require conversion to glucarolactone.
Curley
R W
RW
Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Ohio State University, Columbus 43210.
Humphries
K A
KA
Koolemans-Beynan
A
A
Abou-Issa
H
H
Webb
T E
TE
D001943:Breast Neoplasms; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D004357:Drug Synergism; D005260:Female; D005937:Glucaric Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D012176:Retinoids / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
C087347:2,3,4,5-tetra-O-methylglucaric acid; D012176:Retinoids; D005937:Glucaric Acid