Antibiotic C3368-A, a fungus-derived nucleoside transport inhibitor, potentiates the activity of antitumor drugs.
Antibiotic C3368-A (CA) is produced by a fungus strain from a soil sample collected in Antarctica. CA markedly inhibited radiolabeled thymidine and uridine transport in mouse Ehrlich carcinoma cells, its 50% inhibitory concentration (IC50) being 4.6 and 7.7 microM, respectively. In clonogenic assay, CA displayed a synergistic effect with methotrexate (MTX), mitomycin C (MMC), 5-fluorouracil (5FU), and Adriamycin (ADR) against human oral epidermoid carcinoma KB cells. CA also markedly enhanced the inhibitory effect of 5FU and ADR on the proliferation of human hepatoma BEL-7402 cells as determined by the p-nitrophenyl-N-acetyl-beta-D-glucosaminide (NAG) enzyme-reaction assay. 5FU or ADR cytotoxicity was not augmented by CA in human fetal lung 2BS cells. In vivo, CA significantly potentiated the inhibitory effect of MMC against colon carcinoma 26 in mice. No significant augmentation of toxicity by the combination was found in treated mice. The results suggest that CA, the newly found nucleoside-transport inhibitor, may be useful in potentiation of the effect of antitumor drugs.
Su
J
J
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Tiantan, Beijing.
Zhen
Y C
YC
Qi
C Q
CQ
Hu
J L
JL
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology / Q000633:toxicity*; D000970:Antineoplastic Agents / Q000633:toxicity*; D001572:Benzofurans / Q000494:pharmacology* / Q000627:therapeutic use; D001692:Biological Transport / Q000187:drug effects; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004317:Doxorubicin / Q000633:toxicity; D004357:Drug Synergism; D005260:Female; D005472:Fluorouracil / Q000633:toxicity; D006801:Humans; D007624:KB Cells; D008113:Liver Neoplasms; D008727:Methotrexate / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C; D016685:Mitomycin / Q000627:therapeutic use / Q000633:toxicity; D013141:Spiro Compounds; D013936:Thymidine / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay; D014529:Uridine / Q000378:metabolism*
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D001572:Benzofurans; D013141:Spiro Compounds; C035076:bisdechlorogeodin; D016685:Mitomycin; D004317:Doxorubicin; D005472:Fluorouracil; D013936:Thymidine; D014529:Uridine; D008727:Methotrexate