title: 5-Methyl phenazine-1-carboxylic acid: a novel bioactive metabolite by a rhizosphere soil bacterium that exhibits potent antimicrobial and anticancer activities.
abstract: 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 mitochondrial intrinsic pathway via activation of caspase-3 and down regulation of Bcl-2 protein.
authors.affiliation: Department of Biotechnology, School of Life Sciences, Pondicherry University, Kalapet, Puducherry 605014, India.
authors.forename: R Kamaraj
authors.initials: RK
authors.lastname: Kennedy
authors.affiliation: Department of Biotechnology, School of Life Sciences, Pondicherry University, Kalapet, Puducherry 605014, India.
authors.forename: P Ravindra
authors.initials: PR
authors.lastname: Naik
authors.affiliation: Department of Biotechnology, School of Life Sciences, Pondicherry University, Kalapet, Puducherry 605014, India.
authors.forename: V
authors.initials: V
authors.lastname: Veena
authors.affiliation: Centre for Biotechnology, Anna University, Chennai 600113, Tamil Nadu, India.
authors.forename: B S
authors.initials: BS
authors.lastname: Lakshmi
authors.affiliation: Center for Bioinformatics, School of Life Sciences, Pondicherry University, Kalapet, Puducherry 605014, India.
authors.forename: Pragna
authors.initials: P
authors.lastname: Lakshmi
authors.affiliation: Center for Bioinformatics, School of Life Sciences, Pondicherry University, Kalapet, Puducherry 605014, India.
authors.forename: R
authors.initials: R
authors.lastname: Krishna
authors.affiliation: Department of Biotechnology, School of Life Sciences, Pondicherry University, Kalapet, Puducherry 605014, India. Electronic address: puns2005@gmail.com.
authors.forename: N
authors.initials: N
authors.lastname: Sakthivel
mesh_terms: D000890:Anti-Infective Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D010619:Phenazines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016958:Pseudomonas putida / Q000737:chemistry* / Q000302:isolation & purification; D058441:Rhizosphere
chemical_list: D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D010619:Phenazines; D019253:Proto-Oncogene Proteins c-bcl-2; C037165:1-phenazinecarboxylic acid; D053148:Caspase 3
keywords: 5-Methyl phenazine-1-carboxylic acid betaine; Bcl-2 family proteins; Cytotoxic activity; Pseudomonas putida