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 mu g/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 heliqu inomycin concentration of 50 mu g/ml. The topoisomerase II and I enzym es were inhibited at 30 mu g/ml and 100 mu g/ml of heliquinomycin, res pectively. 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 mu g/ml. In addition, the growth of adriamycin and cisplatin resistant P3 88 cell lines were inhibited at similar concentrations. Heliquinomycin inhibited both DNA and RNA synthesis in cell culture but did not inhi bit protein synthesis. HeLa S3 cells were arrested at the G(2)/M phase by heliquinomycin. These studies suggest that heliquinomycin is a sel ective inhibitor of a cellular DNA helicase and in turn, inhibits grow th of tumor cell lines.