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,...

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Bibliographic Details
Published inAnticancer research Vol. 13; no. 6A; p. 2095
Main Authors Webb, T E, Abou-Issa, H, Stromberg, P C, Curley, Jr, R C, Nguyen, M H
Format Journal Article
LanguageEnglish
Published Greece 01.11.1993
Subjects
9,10-Dimethyl-1,2-benzanthracene - administration & dosage
9,10-Dimethyl-1,2-benzanthracene - toxicity
Adenocarcinoma - chemically induced
Adenocarcinoma - drug therapy
Adenocarcinoma - pathology
Administration, Oral
Animals
Breast Neoplasms - drug therapy
Breast Neoplasms - pathology
Cell Division - drug effects
Cell Line
Delayed-Action Preparations
Drug Interactions
Estradiol - pharmacology
Female
Fenretinide - therapeutic use
Glucaric Acid - therapeutic use
Humans
Mammary Neoplasms, Experimental - chemically induced
Mammary Neoplasms, Experimental - drug therapy
Mammary Neoplasms, Experimental - pathology
Mice
Mice, Nude
Ovariectomy
Protein Kinase C - metabolism
Rats
Rats, Sprague-Dawley
Transplantation, Heterologous
Tumor Cells, Cultured
Vitamin A Deficiency - pathology
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Summary: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.
ISSN:0250-7005