Effects Of Enediyne Antitumor Antibiotic C1027 On The Induction Of Apoptosis And On Oncogene Expression In Cancer Cells

The new antitumor antibiotic C1027 produced by Streptomyces globisporous C-1027 was discovered during the screening of microbial metabolites. Antibiotic C1027, containing an acid protein of 110 amino acid residues and a chromophore of novel enediyne structure, showed extremely potent cytotoxicity toward cultured cancer cells and markedly inhibited the growth of transplantable tumors in mice. Compared in terms of IC50 values, C1027 showed much more potent cytotoxicity than doxorubicin, mitomycin and necarzinostatin. As determined by tritium-labeled precursor incorporation assay, C1027 strongly inhibited DNA and RNA syntheses in hepatoma BEL-7402 cells without affecting protein synthesis. C1027 and its chromphore caused directly double or single strand breaks on purified DNA without any supplement of reducing agents. C1027 delayed the progression of hepatoma BEL-7402 cells through the S-phase and blocked the cells at G2+M.Enediyne antitumor antibiotics are currently the focus of intense research activity in the fields of chemistry, biology, and medical sciences because of their unusual molecular structure and potent biological activities. In this study, we further investigated C1027-induced apoptosis in HL-60 cells, effects of C1027 on oncogene expression and gene-specific DNA damage, C1027-caused DNA damage and repair, as well as the effect of C1027 on cytoskeleton in BEL-7402 cells. Results...