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Anti-glioma Natural Products Downregulating Tumor Glycolytic Enzymes from Marine Actinomycete Streptomyces sp. ZZ406.

ABSTRACT: Marine natural products are important resources for discovering novel anticancer drugs. In this study, an extract prepared from the culture of a sea anemone-derived actinomycete Streptomyces sp. ZZ406 in soluble starch and casein-related liquid medium was found to have activity in inhibiting the proliferation of glioma cells and reducing the production of lactate in glioma cells. Chemical investigation of this active crude extract resulted in the isolation of four new compounds and seven known ones. Structures of the new compounds were determined by a combination of extensive NMR analyses, HRESIMS and MS-MS data, electronic circular dichroism calculation, chemical degradation, and Marfey's method. New compound 1 showed potent activity against the proliferation of different glioma cells with IC50 values of 4.7 to 8.1??M, high selectivity index (>12.3 to 21.3), and good stability in human liver microsomes. Western blot analysis revealed that compound 1 remarkably downregulated the expressions of several important glioma glycolytic enzymes. The data from this study suggested that compound 1 might have potential as a novel anti-glioma agent to be further investigated.

SUBMITTER: Chen M

PROVIDER: S-EPMC5758648 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Project description:ObjectiveTo investigate the cytotoxic activity of actinomycete isolated from marine sediment.MethodsIn the present study the DNA was isolated and the ITS region of 16s rRNA was amplified by polymerase chain reaction, using two universal bacterial primers, 1492R (5'-GGTTACCTTGTTAC GACTT-3') and Eubac27F (5'-AGAGTTTGATCCTGGCTC AG-3'). The amplified products were purified using TIANgel mini purification kit, ligated to MD18-T simple vector (TaKaRa), and transformed into competent cells of Escherichia coli DH5α. 16S rRNA gene fragment was sequenced using forward primer M13F (-47) and reverse primer M13R (-48). Blast search sequence similarity was found against the existing non-redundant nucleotide sequence database thus, identified as Streptomyces sp SU, Streptomyces rubralavandulae strain SU1, Streptomyces cacaoi strain SU2, Streptomyces cavourensis strain SU3, Streptomyces avidinii strain SU4, Streptomyces globisporus strain SU5, Streptomyces variabilis strain SU6, Streptomyces coelicolor strain SU 7. Among the eight identified isolates, one actinomycete Streptomyces avidinii strain SU4 was selected for further study.ResultsCrude extract of the actinomycete isolate exhibited IC50 in 64.5 µg against Hep-2 cell line, 250 µg in VERO cell line. This value is very close to the criteria of cytotoxicity activity for the crude extracts, as established by the American National Cancer Institute (NCI) is in IC50 < 30 µg/mL. The GC MS analysis showed that the active principle might be 1,2-benzenedicarboxylic acid, bis(2-methylpropyl) ester (12.17%), isooctyl phthalate (15.29%) with the retention time 15.642 and 21.612, respectively.ConclusionsThis study clearly proves that the marine sediment derived actinomycetes with bioactive metabolites can be expected to provide high quality biological material for high throughout biochemical and anticancer screening programs. These results help us to conclude that the potential of using metabolic engineering and post genomic approaches to isolate more bioactive compounds and make their possible commercial application is not far off.

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Anti-glioma Natural Products Downregulating Tumor Glycolytic Enzymes from Marine Actinomycete Streptomyces sp. ZZ406.

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