期刊
CHEMICO-BIOLOGICAL INTERACTIONS
卷 231, 期 -, 页码 71-82出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.cbi.2015.03.002
关键词
Pseudomonas putida; 5-Methyl phenazine-1-carboxylic acid betaine; Cytotoxic activity; Bcl-2 family proteins
资金
- Department of Biotechnology, Ministry of Science and Technology, Government of India through BUILDERS programme
A new rhizosphere soil bacterium that exhibits antimicrobial potential against human pathogens was isolated. On the basis of 16S ribosomal RNA nucleotide sequence homology and subsequent phylogenetic tree analysis, the strain PUW5 was identified as Pseudomonas putida. A bioactive metabolite was extracted and purified using silica gel column chromatography and preparative HPLC. Characterization of metabolite was done by employing Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR) and mass spectroscopy (MS). On the basis of spectroscopic data, the metabolite was structurally elucidated as 5-methyl phenazine-1-carboxylic acid betaine (MPCAB). The MPCAB exhibits selective cytotoxicity towards lung (A549) and breast (MDA MB-231) cancer cell lines in dose-dependent manner with IC50 value of 488.7 +/- 2.52 nM and 458.6 +/- 2.48 nM respectively. The MPCAB exhibited inhibition of cell viability, DNA synthesis, induced G1 cell cycle arrest and apoptosis in cancer cells. The docking and interaction studies confirmed the binding potential of MPCAB with Bcl-2 than Bcl-xL and Bcl-w proteins. These results strongly suggest that the MPCAB induces apoptosis in A549 and MDA MB-231 cancer cells through mitochondria] intrinsic pathway via activation of caspase-3 and down regulation of Bcl-2 protein. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
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