Thioviridamide, a novel apoptosis inducer in transformed cells from Streptomyces olivoviridis.
In the course of screening for antitumor antibiotics using 3Y1 rat fibroblasts transformed with adenovirus oncogenes, a new active substance designated thioviridamide was isolated from the culture broth of an actinomycete. The producing organism was identified as Streptomyces olivoviridis on the basis of its culture characteristics and physiological properties. Thioviridamide showed cytotoxicity selectively against Ad12-3Y1 cells (IC50 = 3.9 ng/ml) and E1A-3Y1 cells (IC50 = 32 ng/ml), both of which contain the adenovirus E1A oncogene. Significant numbers of Ad12-3Y1 cells treated with thioviridamide contained condensed chromatin and fragmented nuclei, indicating that thioviridamide induced apoptosis.
Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan. hykw@rs.noda.tus.ac.jp
Yoichi
Y
Hayakawa
Kahori
K
Sasaki
Hisashi
H
Adachi
Keiko
K
Furihata
Koji
K
Nagai
Kazuo
K
Shin-ya
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000096:biosynthesis / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D045744:Cell Line, Tumor; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003470:Culture Media; D005285:Fermentation; D005347:Fibroblasts / Q000187:drug effects; D010456:Peptides, Cyclic / Q000096:biosynthesis / Q000494:pharmacology*; D051381:Rats; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D013302:Streptomyces / Q000737:chemistry / Q000145:classification / Q000378:metabolism*; D013778:Tetrazolium Salts; D013844:Thiazoles; D013854:Thioamides / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D003470:Culture Media; D010456:Peptides, Cyclic; D013778:Tetrazolium Salts; D013844:Thiazoles; D013854:Thioamides; C509635:thioviridamide; C022616:thiazolyl blue