Mechanism of growth inhibition of mammary carcinomas by glucarate and the glucarate: retinoid combination.
In synergistic combination 0.75 mmol/kg diet of N-(4-hydroxyphenyl) retinamide and 32 mmol/kg diet of glucarate inhibits the growth of primary rat mammary tumors, but are equally effective as single agents at 1.5 and 128 mmol/kg diet, respectively. Dose-response studies suggest that like retinoids, glucarate acts directly on tumor cells, rather than having an adjuvant effect. Although synergism is maintained down to at least 0.38 mmol/kg diet of the retinoid, experiments using Vitamin A-deficient diets indicates 128 mmol/kg glucarate acts independent of retinoid. Both alone and in combination, glucarate and retinoid inhibited the growth of human mammary tumor cells grown in the athymic mouse, the growth of rat mammary tumors in germfree rats and the hormone-independent MTW 9a/R rat mammary tumor. Like retinoids, glucarate suppresses protein kinase C and induces transforming growth factor-beta, in the mammary tumor cells.
Webb
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TE
Department of Medical Biochemistry, College of Medicine, Ohio State University, Columbus 43210.
Abou-Issa
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H
Stromberg
P C
PC
Curley
R C
RC
Nguyen
M H
MH
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000008:administration & dosage / Q000633:toxicity; D000230:Adenocarcinoma / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D000284:Administration, Oral; D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003692:Delayed-Action Preparations; D004347:Drug Interactions; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D017313:Fenretinide / Q000627:therapeutic use*; D005937:Glucaric Acid / Q000627:therapeutic use*; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D010052:Ovariectomy; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D014802:Vitamin A Deficiency / Q000473:pathology
D003692:Delayed-Action Preparations; D017313:Fenretinide; D004958:Estradiol; D015127:9,10-Dimethyl-1,2-benzanthracene; D011493:Protein Kinase C; D005937:Glucaric Acid