Effect of a Novel Antibiotic, Heliquinomycin, on DNA Helicase and Cell Growth

Abstract

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 μg/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 μg/ml. The topoisomerase II and I enzymes were inhibited at 30 μg/ml and 100 μg/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 μg/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.