1988 年 108 巻 12 号 p. 1129-1140
New anticancer agents and oncogene function inhibitors isolated from microorganisms in Institute of Microbial Chemistry are reviewed.
Aclacinomycin found in 1975 is a less toxic and non-mutagenic anthracycline. It is now in clinical use mainly for acute nonlymphocytic leukaemia. Tetrahydropyranyl-adriamycin was synthesized in 1979 as a structural analogue of baumycin, and proved to be effective in inhibiting leukaemias and various solid tumours in patients. FAD-104 is a new semisynthetic anthracycline consisting of the 14-hemipimelate derivative of adriamycinone and 2, 6-dideoxy-2-fluoro-a-L-talopyranose. It shows apparently stronger antitumour activity than adriamycin against L 1210 mouse leukaemia. It is effective over a very broad range. Liblomycin is a derivative of bleomycin, which is clinically used mainly for squamous cell carcinoma but has pulmonary toxicity. Liblomycin shows much less pulmonary toxicity than bleomycin and potent antitumour activity in animals. Spergualin and 15-deoxyspergualin are new anticancer agents with unique structures. They showed potent antitumour activity against many experimental leukaemias and some solid tumours. Their mechanism of antitumour action may include induction of tumour cell immunity.
More than 40 oncogenes have been identified. Many of them are considered to act through tyrosine kinase activity. Erbstatin was isolated as an inhibitor of tyrosine kinase associated with epidermal growth factor receptor. It also inhibits tyrosine kinase of src oncogene product. Herbimycin inhibits src oncogene functions. It changes the morphology of src-transformed cells into the normal morphology. Oxanosine inhibits ras oncogene functions. It changes the phenotypes of K-rasts-NRK cells completely into the normal phenotypes by decreasing the intracellular levels of guanine nucleotides. Various oncogenes induces activation of cellular phosphatidylinositol turnover. We have isolated psi-tectorigenin, an isoflavonoid, as an inhibitor of phosphatidylinositol turnover.