Chemotherapeutic evaluation of glucarate and N-(4-hydroxyphenyl)retinamide alone and in combination in the rat mammary tumor model.
We evaluated calcium glucarate (CGT) and N-(4-hydroxyphenyl)retinamide (HPR) for their effectiveness as anti-tumor agents. For this evaluation, we tested the effects of CGT and HPR given alone or combined in the diet on the growth of established 7,12-dimethylbenz[a]anthracene-induced rat mammary tumors. When given alone, optimal doses of CGT (128.0 mmol/kg in the diet) or HPR (2.0 mmol/kg in the diet) administered daily for 25 days reduced mammary tumor sizes by approximately 15% or 20%, respectively. Suboptimal doses of CGT (64.0 mmol/kg) or HPR (0.75 mmol/kg) administered daily for 25 days only slightly inhibited tumor growth; over the 25-day period, the tumor sizes in rats on the CGT diet and in rats on the HPR diet increased by 55% and 70%, respectively, compared with a 98% increase in tumor sizes in the rats on the control diet. In contrast, the combination of suboptimal doses of CGT (64.0 mmol/kg) and HPR (0.75 mmol/kg) administered daily for 25 days decreased tumor sizes by 33%. These results are statistically significant. They show that CGT and HPR act synergistically. Consequently, lower concentrations of these agents can be used to inhibit mammary tumor development and growth.
Abou-Issa
H
H
Department of Surgery, Ohio State University, Columbus 43210.
Webb
T E
TE
Minton
J P
JP
Moeschberger
M
M
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004357:Drug Synergism; D005260:Female; D017313:Fenretinide; D005937:Glucaric Acid / Q000008:administration & dosage; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D011919:Rats, Inbred Strains; D014212:Tretinoin / Q000008:administration & dosage / Q000031:analogs & derivatives
D017313:Fenretinide; D014212:Tretinoin; D015127:9,10-Dimethyl-1,2-benzanthracene; D005937:Glucaric Acid