Basis for the anti-tumor and chemopreventive activities of glucarate and the glucarate:retinoid combination.
The biochemical basis for the cancer chemopreventive and anti-cancer activities of glucarate, retinoids (13-cis-retinoic acid, hydroxyphenyl retinamide) and their synergistic combination, has been evaluated. Neither alone nor in combination did these agents affect the level in the rat, of enzymes which are (a) known to correlate with reduced risk of carcinogenesis (detoxification enzyme, catalase, glutathione reductase) nor (b) enzymes which correlate with increased risk of carcinogenesis (beta-glucuronidase, xanthine oxidase, glucose-6-phosphate dehydrogenase). Retinoids, but neither glucarate nor its lactone inhibited free radical-induced lipid peroxidation. Both agents alone and synergistically in combination, raise cellular cAMP levels, repress protein kinase C and more generally inhibited DNA synthesis.
Abou-Issa
H
H
Department of Surgery, Ohio State University, Columbus 43210.
Dwivedi
C
C
Curley
R W
RW
Kirkpatrick
R
R
Koolemans-Beynen
A
A
Engineer
F N
FN
Humphries
K A
KA
el-Masry
W
W
Webb
T E
TE
D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000517:prevention & control*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004357:Drug Synergism; D005260:Female; D005937:Glucaric Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy / Q000201:enzymology / Q000517:prevention & control; D011230:Precancerous Conditions / Q000188:drug therapy / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012176:Retinoids / Q000008:administration & dosage / Q000627:therapeutic use*; D013936:Thymidine / Q000378:metabolism; D014212:Tretinoin / Q000627:therapeutic use; D014316:Tritium; D014407:Tumor Cells, Cultured / Q000187:drug effects
D016588:Anticarcinogenic Agents; D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D012176:Retinoids; D014316:Tritium; D014212:Tretinoin; D005937:Glucaric Acid; D013936:Thymidine