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In vitro antiproliferative, pro-apoptotic, antimetastatic and anti-inflammatory potential of 2,4-diacteylphloroglucinol (DAPG) by Pseudomonas aeruginosa strain FP10

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Abstract

The 2,4-diacteylphloroglucinol (DAPG), a polyketide metabolite extracted from Pseudomonas aeruginosa strain FP10, exhibited selective cytoxicity against lung (A549), breast (MDA MB-231), cervical (HeLa) and colon (HCT-15) cancer cells in differential and dose-dependent manner. The anticancer and antimetastatic activities of DAPG were mediated by the inhibition of ROS, NF-κB, Bcl-2, MMP-2, VEGF and primary inflammatory mediators such as TNF-α, IL-6, IL-1β and NO. The DAPG induced apoptosis in cancer cells by intrinsic and extrinsic pathways via the release of cytochrome-C, upregulation of Bax and the activation of caspases and also, exhibited anti-inflammatory activity by the inhibition of LPS-inflammed cell proliferation of macrophage (Raw 264.7), monocytic cells (THP-1) and peripheral blood mononuclear cells (PBMCs). Results further confirmed that the DAPG inhibited the primary inflammatory mediators in cancer cells and inflammed immune cells through the down regulation of NF-κB. In the present study, for the first time, antiproliferative, proapoptotic, antimetastatic and anti-inflammatory activities of DAPG in various cancer cells and inflammation-induced immune cells have been reported.

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Abbreviations

AO:

Acridine orange

Bax:

Bcl-2 associated X-protein

Bcl-2:

B-cell lymphoma 2

CRI:

Cancer-related inflammation

DCF:

2,7-Dichlorofluorescein

DCFDA:

2,7-Dichlorofluorescein diacetate

DMEM:

Dulbecco’s modified eagle medium

RPMI:

Rosewell park memorial institute

EB:

Ethidium bromide

FBS:

Fetal bovine serum

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

IL-1:

Interleukin-1

IL-1β:

Interleukin-1 beta

IL-6:

Interleukin-6

JSH:

23-4-Methyl-N1-(3-phenyl-propyl)-benzene-1,2-diamine

LDH:

Lactate dehydrogenase

LPS:

Lipopolysaccharride

MTT:

3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide

NO:

Nitric oxide

PE:

Phycoerthyrin

PI:

Propidium iodide

PPM:

Pigment producing media

RNase:

Ribonulease

ROS:

Reactive oxygen species

VEGF:

Vascular endothelial growth factor

VRSA:

Vancomycin resistant Staphylococcus aureus

VSV:

Vascular stomatitis viruses (VSV-1)

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Acknowledgments

The joint University Grant Commission-Council for Scientific and Industrial Research (joint UGC-CSIR), Government of India, New Delhi through a research fellowship to Ms. V. Veena and the financial support from the Department of Biotechnology (DBT), New Delhi and University Grants Commission-Special Assistance Programme (UGC-SAP) coordinated by Prof. N. Sakthivel are gratefully acknowledged.

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  1. Department of Biotechnology, School of Life Sciences, Pondicherry University, Kalapet, Puducherry, 605014, India

    Vijay Kumar Veena, Ravindra Naik Popavath, Kamaraj Kennedy & Natarajan Sakthivel

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  1. Vijay Kumar Veena
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Correspondence to Natarajan Sakthivel.

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Veena, V.K., Popavath, R.N., Kennedy, K. et al. In vitro antiproliferative, pro-apoptotic, antimetastatic and anti-inflammatory potential of 2,4-diacteylphloroglucinol (DAPG) by Pseudomonas aeruginosa strain FP10. Apoptosis 20, 1281–1295 (2015). https://doi.org/10.1007/s10495-015-1162-9

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