Effect of a novel antibiotic, heliquinomycin, on DNA helicase and cell growth.
Heliquinomycin, a novel microbial product, was found to inhibit a human DNA helicase enzyme isolated from HeLa S3 cells at concentrations of 5 to 10 micrograms/ml. In contrast, adriamycin, etoposide and cisplatin did not inhibit this enzyme at the concentrations tested. Furthermore, the replication and repair of SV40 chromosome were not affected at heliquinomycin concentration of 50 micrograms/ml. The topoisomerase II and I enzymes were inhibited at 30 micrograms/ml and 100 micrograms/ml of heliquinomycin, respectively. Heliquinomycin inhibited the growth of HeLa S3, KB, LS180, K562 and HL60 human tumor cell lines at IC50 values of 0.96 to 2.8 micrograms/ml. In addition, the growth of adriamycin and cisplatin resistant P388 cell lines were inhibited at similar concentrations. Heliquinomycin inhibited both DNA and RNA synthesis in cell culture but did not inhibit protein synthesis. HeLa S3 cells were arrested at the G2/M phase by heliquinomycin. These studies suggest that heliquinomycin is a selective inhibitor of a cellular DNA helicase and in turn, inhibits growth of tumor cell lines.
Institute of Microbial Chemistry, Tokyo Japan.
M
M
Chino
K
K
Nishikawa
A
A
Yamada
M
M
Ohsono
T
T
Sawa
F
F
Hanaoka
M
M
Ishizuka
T
T
Takeuchi
D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000494:pharmacology*; D016227:Benzoquinones / Q000737:chemistry / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002474:Cell-Free System; D004247:DNA / Q000187:drug effects; D004265:DNA Helicases / Q000037:antagonists & inhibitors*; D004260:DNA Repair; D004261:DNA Replication / Q000187:drug effects; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006868:Hydrolysis; D015394:Molecular Structure; D013141:Spiro Compounds / Q000737:chemistry / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D016227:Benzoquinones; D004791:Enzyme Inhibitors; D013141:Spiro Compounds; C101772:heliquinomycin; D004247:DNA; D004265:DNA Helicases; D004264:DNA Topoisomerases, Type I