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Antitumor compounds from Streptomyces sp. KML-2, isolated from Khewra salt mines, Pakistan

BACKGROUND: Actinomycetes are gram positive bacteria with high G + C content in their DNA and are capable of producing variety of secondary metabolites. Many of these metabolites possess different biological activities and have the potential to be developed as therapeutic agents. The aim of the pres...

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Autores principales: Aftab, Usman, Zechel, David L., Sajid, Imran
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4607010/
https://www.ncbi.nlm.nih.gov/pubmed/26466995
http://dx.doi.org/10.1186/s40659-015-0046-3
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author Aftab, Usman
Zechel, David L.
Sajid, Imran
author_facet Aftab, Usman
Zechel, David L.
Sajid, Imran
author_sort Aftab, Usman
collection PubMed
description BACKGROUND: Actinomycetes are gram positive bacteria with high G + C content in their DNA and are capable of producing variety of secondary metabolites. Many of these metabolites possess different biological activities and have the potential to be developed as therapeutic agents. The aim of the present study was to screen actinomycetes inhabiting halophilic environment such as Khewra salt mines present in Pakistan for cytotoxic and antitumor compounds. RESULTS: An actiomycetes strain designated as Streptomyces sp. KML-2 was isolated from a saline soil of Khewra salt mines, Pakistan. The strain Streptomyces sp. KML-2 showed 84 % cytotoxic activity against larvae of Artemia salina. In the screening phase, the strain exhibited significant antitumor activity with IC(50) values of 12, 48 and 56 µg/ml against Hela, MDBK and Vero cell lines, respectively. After that extract from 20 l fermentation was used to purify secondary metabolites by several chromatographic techniques. Structure elucidation of isolated compounds revealed that it is highly stable producer of Chromomycin SA (1) and 1-(1H-indol-3-yl)-propane-1,2,3-triol (2). Both of the isolated compounds showed significant antitumor activity against Hela and MCF-7 cancer cell lines (IC(50) values 8.9 and 7.8 µg/ml against Hela; 12.6 and 0.97 µg/ml against MCF-7, respectively). The 16S rRNA gene sequence (1437 bp) of the strain confirm its identity (99 %) with Streptomyces griseus. CONCLUSIONS: From this research work we were successful in isolating two potent antitumor compounds, Chromomycin SA and 1-(1H-indol-3-yl)-propane-1,2,3-triol from Streptomyces KML-2 strain, isolated from Khewra salt mine. As such this is the second report which confirms that S. griseus can produce Chromomycin SA without introducing any mutagenesis in its biosynthesizing gene cluster and isolated indole derivative is being reported first time from any member of actinomycetes group with having novel antitumor activity against Hela and MCF-7 cells. Nucleotide sequences: Nucleotide sequence data reported are available in the GenBank database under the accession number: GenBank KJ009562. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40659-015-0046-3) contains supplementary material, which is available to authorized users.
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spelling pubmed-46070102015-10-16 Antitumor compounds from Streptomyces sp. KML-2, isolated from Khewra salt mines, Pakistan Aftab, Usman Zechel, David L. Sajid, Imran Biol Res Regular Article BACKGROUND: Actinomycetes are gram positive bacteria with high G + C content in their DNA and are capable of producing variety of secondary metabolites. Many of these metabolites possess different biological activities and have the potential to be developed as therapeutic agents. The aim of the present study was to screen actinomycetes inhabiting halophilic environment such as Khewra salt mines present in Pakistan for cytotoxic and antitumor compounds. RESULTS: An actiomycetes strain designated as Streptomyces sp. KML-2 was isolated from a saline soil of Khewra salt mines, Pakistan. The strain Streptomyces sp. KML-2 showed 84 % cytotoxic activity against larvae of Artemia salina. In the screening phase, the strain exhibited significant antitumor activity with IC(50) values of 12, 48 and 56 µg/ml against Hela, MDBK and Vero cell lines, respectively. After that extract from 20 l fermentation was used to purify secondary metabolites by several chromatographic techniques. Structure elucidation of isolated compounds revealed that it is highly stable producer of Chromomycin SA (1) and 1-(1H-indol-3-yl)-propane-1,2,3-triol (2). Both of the isolated compounds showed significant antitumor activity against Hela and MCF-7 cancer cell lines (IC(50) values 8.9 and 7.8 µg/ml against Hela; 12.6 and 0.97 µg/ml against MCF-7, respectively). The 16S rRNA gene sequence (1437 bp) of the strain confirm its identity (99 %) with Streptomyces griseus. CONCLUSIONS: From this research work we were successful in isolating two potent antitumor compounds, Chromomycin SA and 1-(1H-indol-3-yl)-propane-1,2,3-triol from Streptomyces KML-2 strain, isolated from Khewra salt mine. As such this is the second report which confirms that S. griseus can produce Chromomycin SA without introducing any mutagenesis in its biosynthesizing gene cluster and isolated indole derivative is being reported first time from any member of actinomycetes group with having novel antitumor activity against Hela and MCF-7 cells. Nucleotide sequences: Nucleotide sequence data reported are available in the GenBank database under the accession number: GenBank KJ009562. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40659-015-0046-3) contains supplementary material, which is available to authorized users. BioMed Central 2015-10-14 /pmc/articles/PMC4607010/ /pubmed/26466995 http://dx.doi.org/10.1186/s40659-015-0046-3 Text en © Aftab et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Regular Article
Aftab, Usman
Zechel, David L.
Sajid, Imran
Antitumor compounds from Streptomyces sp. KML-2, isolated from Khewra salt mines, Pakistan
title Antitumor compounds from Streptomyces sp. KML-2, isolated from Khewra salt mines, Pakistan
title_full Antitumor compounds from Streptomyces sp. KML-2, isolated from Khewra salt mines, Pakistan
title_fullStr Antitumor compounds from Streptomyces sp. KML-2, isolated from Khewra salt mines, Pakistan
title_full_unstemmed Antitumor compounds from Streptomyces sp. KML-2, isolated from Khewra salt mines, Pakistan
title_short Antitumor compounds from Streptomyces sp. KML-2, isolated from Khewra salt mines, Pakistan
title_sort antitumor compounds from streptomyces sp. kml-2, isolated from khewra salt mines, pakistan
topic Regular Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4607010/
https://www.ncbi.nlm.nih.gov/pubmed/26466995
http://dx.doi.org/10.1186/s40659-015-0046-3
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