ANGUINOMYCIN-C AND ANGUINOMYCIN-D, NEW ANTITUMOR ANTIBIOTICS WITH SELECTIVE CYTOTOXICITY AGAINST TRANSFORMED-CELLS

The retinoblastoma protein (pRB) is inactivated during the development of a wide variety of human cancers. In the course of our screening for antitumor antibiotics by using pRB-inactivated cells, an actinomycete strain was found to produce two active substances, which were elucidated to be new members of the leptomycin-anguinomycin family by NMR spectral analysis and were designated anguinomycins C and D. The anguinomycins induced growth arrest against normal cells and induced cell death against transformed cells, in which pRB was inactivated by viral oncoproteins such as human papillomavirus E7, adenovirus E1A and simian virus 40 large T antigen.