Streptomyces 4209-23 Anti-tumor Activity Of The Composition And Microbial Source Of Il-4 Receptor Antagonist

Microorganism products have been regarded as important sources that could produce antitumor antibiotics since the first anticancer drug was found in 1950s.Here we used the methods of paraU-bacteria and spermatogonium as the screening model and an actinomycete strain 4209-23 was isolated from a soil sample in Yunnan province which showed inhibitory activity on spermatogonium and bacteria.Based on the culture and physiological characteristics as well as the investigation of the molecular genetics, Strain 4209-23 was found to resemble Streptomyces albofaciens, so it was a new strain.A compound 4209-23A was isolated from the fermentation broth of the Streptomyces 4209-23. By extensive studies of its UV,IR,MS,1^H-NMR,(13)^C-NMR,HMQC and HMBC spectra, the structure of 4209-23A was identified as a known compound streptonigrin. Its chemical name isβ-D-Glucopyranuronic acid, methyl ester, 2,3,4-triacetate 1-[[4-(hydroxymethyl)-2-nitrophenyl]carbamate].Streptonigrin had activity for both of Gram-positive bacterias and Gram-negative bacterias. And it showed anti-tumor activities. Interleukin-4(IL-4) is a pleiotropic type I cytokine produced by activated T cells, mast cells, and basophils. It is considered important in the development of allergic inflammation and airway hyperresponsiveness(AHR). The overlap of its function results from the IL-4R-chain forming an important functional signaling component of both the IL-4 and IL-13 receptors. Consequently, inhibition of the receptor-ligand interaction may offer an effective way to interfere the biological effect of IL-4.With the recombinant IL-4R as target, an ELISA assay for screening antagonists of IL-4R was developed by our lab. Using this method, we found two strains named 4849 and 4318 which had activity in this assay.Based on the culture and physiological characteristics as well as the investigation of the molecular genetics, strain 4849 was found to resemble Streptomyces thioluteus, so it was named Streptomyces thioluteus.Eight compounds 4849A-G and 4318A were isolated from the fermentation broth of the Streptomyces 4849 and the Streptomyces 4318. In this screening model, we found 4849C-G and 4318A had activity. The molecular formular and structure of them were elucidatited through UV,IR,MS,1^H-NMR,(13)^C-NMR,HMQC and HMBC spectra. 4849F was identified a new structure.In addition, 4849F has no activity for both of Gram-positive bacterias and Gram-negative bacterias. The MTT assays showed that the novel compound 4849F has anti-tumor activities for human breast cancer MCF-7 and human ovarian cancer A2780 cell lines with IC₅₀ 6.78μM and 5.57μM respectively.