[A fungus-derived novel nucleoside transport inhibitor potentiates the activity of antitumor drugs].
Antibiotic C3368-B (CB), identified as 3,9-dihydroxy-1-methoxy-7-methylanthraquinone, is produced by a fungus strain, Chrysosporium verrucosum Tubaki, isolated from a soil sample collected from Antarctica. CB was found to be a highly-active nucleoside transport inhibitor. By radiolabelled nucleoside assay, CB was shown to markedly inhibit thymidine and uridine transport in Ehrlich carcinoma cells, with IC50 values of 7.5 and 9.6 mumol.L-1 respectively. CB showed fairly low cytotoxicity to tumor cells. The IC50 values for epidermoid cancer KB cells and hepatoma BEL-7402 cells in clonogenic assay was 77 and 69 mumol.L-1. At relatively noncytotoxic concentrations, CB markedly enhanced the cytotoxicity of methotrexate, 5-fluorouracil, mitomycin C against KB cells and BEL-7402 cells. CB was also found to partly reverse the multi-drug resistance to vincristine and actinomycin D in leukemia L1210/MDR cells. The IC50 values were reduced by 4.9-fold (1.75 to 0.36 mumol.L-1) for vincristine and 3.3-fold (0.39 to 0.12 mumol.L-1) for actinomycin D. These results suggest that CB, as a newly-found nucleoside transport inhibitor, may be potentially useful in cancer chemotherapy.
Su
J
J
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing.
Zhen
Y S
YS
Qi
C Q
CQ
Chen
W J
WJ
D000818:Animals; D000880:Anthraquinones / Q000302:isolation & purification / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002912:Chrysosporium / Q000737:chemistry; D004357:Drug Synergism; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D009705:Nucleosides / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000880:Anthraquinones; D000970:Antineoplastic Agents; C092697:C 3368-B; D009705:Nucleosides