[Biological activities of a new antitumor antibiotics]

The antitumor antibiotic sporamycin is composed of polypeptide and non-chromophore subunits and shows remarkable antitumor activity against various animal tumors. The mechanism of action of this compound involves host-mediated antitumor activity as well as direct cytotoxic activity due to the inhibition of nucleic acid synthesis. Pretreatment of mice with sporamycin produced not only a remarkable inhibition of tumor growth but also strengthened the resistance of the host to infection with Pseudomonas aeruginosa. The immunological activity described above was also observed using the isolated polypeptide moiety of sporamycin. The antitumor antibiotic stubomycin possesses a marked cytotoxic activity against mammalian cells in vitro and in vivo. Stubomycin showed inhibitory activity against DNA, RNA and protein synthesis to almost the same degree. It was also shown that these activities were significantly reduced by lipids such as phosphatidylserine, olive oil and cardiolipin. On the other hand, stubomycin did not show any mutagenic effects in mammalian cells or bacteria. It seems that the primary action of stubomycin is due to change and ultimate lysis of the cell surface. It was observed that a new antibiotic, kazusamycin, possessed very strong cytotoxic activity against mammalian cells in vitro. However this compound exhibited no antibacterial activity against gram-positive and gram-negative bacteria. We are presently investigating the biological activities of a monoclonal antibody combined with kazusamycin.