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KMID : 0545119980080050455
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Journal of Microbiology and Biotechnology
1998 Volume.8 No. 5 p.455 ~ p.460
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Aburatubolactam C, a Novel Apoptosis-inducing Substance Produced by Marine Streptomyces sp. SCRC A-20
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Bae, Myung Ae
Kaoru, Yamada/Daisuke, Uemura/Seu, Jung Hwn/Kim, Young Ho
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Abstract
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In the course of screening for new antitumor substances, a novel cytotoxic agent inducing apoptotic cell death was isolated from the culture broth of marine bacterial strain SCRC A-20. Strain SCRC A-20 was separated from a mollusk and was chemotaxonomically identified as a Streptomyces sp. The cytotoxic substance was purified by organic solvent extraction followed by silica gel column chromatography and preparative TLC. HRFAB-MS determined its molecular formula to be C_30H_40N_2O_5 (MW 508). The 1D and 2D NMR spectral data demonstrated that the substance has a novel lactam structure of a 20-membered macrocycle coupled with a unique acyl tetramine and bicyclo[3.3.0] octane, which includes three methyl groups, six olefinic protons, five carbonyl groups, a conjugated diene and a dienone. The substance, named aburatubolactam C, appeared to be cytotoxic for various continuously proliferating tumor cells of human and murine origins. The IC_50 values determined by MTT assay were in the range of 0.3 to 5.8 ㎍/㎖. When Jurkat T cells were treated with 3 ㎍/㎖ of aburatubolactam C, the apoptotic DNA fragmentation was detectable within 3 h, indicating that the cytotoxic effect of aburatubolactam C on tumor cells is attributable to the induced apoptosis.
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