Inhibition of catabolic pathway of 5-fluorouracil by 3-cyano-2,6-dihydroxypyridine in human lung cancer tissues.
Our studies of the degradation and the phosphorylation of 5-fluorouracil (5-FU) in normal and tumor lung tissues from 10 cases of lung cancer have shown that the phosphorylation of 5-FU in the tumor tissues was about 2- to 3-fold higher than that in normal tissues, and that the degradation of 5-FU in tumor tissues was nearly 6-fold higher than that in normal tissues. BOF-A2 is an anti-neoplastic agent newly synthesized from 1-ethoxymethyl-5-FU and 3-cyano-2,6-dihydroxypyridine (CNDP). The inhibitory effect of CNDP on the degradation of 5-FU in the tumor tissues was potent (IC50 3.9 x 10(-9) M). Thus, BOF-A2 exerts its anti-neoplastic effect on tumors by potentiating the action of 5-FU through inhibition of 5-FU degradation by the CNDP moiety.
Okayasu
T
T
Second Department of Surgery, Hokkaido University School of Medicine, Sapporo.
Sugiyama
K
K
Miyauchi
S
S
D000230:Adenocarcinoma / Q000378:metabolism*; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D005260:Female; D005472:Fluorouracil / Q000378:metabolism*; D006801:Humans; D008168:Lung / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology*
D011725:Pyridines; C053195:2,6-dihydroxy-3-cyanopyridine; D005472:Fluorouracil