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2-Deoxy glucose regulate MMP-9 in a SIRT-1 dependent and NFkB independent mechanism

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Abstract

MMP9 is a member of the family of zinc-containing endopeptidases which degrade various components of the extracellular matrix, thereby regulating matrix remodeling. Since matrix remodeling plays an important role during growth and progression of cancer and considering the fact that, tumor cells switch to aerobic glycolysis as its major energy source, this study was designed to analyze if partial inhibition of glycolysis (the major energy pathway during hypoxia) can be used as a means to control matrix remodeling in terms of MMP9 activity and expression. For this, human epithelial carcinoma cells were treated with glycolytic inhibitor, 2-deoxy glucose (2DG) at sub-lethal concentrations followed by analysis of the expression and activity of MMP2 and MMP9. The experimental findings demonstrate that exposure of cancer cells to glycolytic inhibitor at concentration that does not induce ER stress, downregulates the activity and expression of MMP9 without affecting the expression levels and activity of MMP2. Further mechanistic analysis revealed that the regulation of MMP9 was mediated in a SIRT-1 dependent mechanism and did not alter the NFkB signaling pathway. The overall results presented here, therefore suggest that the use of glycolytic inhibitor, 2DG at concentration that do not affect cell viability or induce ER stress can be an effective strategy to control matrix remodeling.

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Abbreviations

2DG:

2-Deoxy glucose

MMP9:

Matrix metalloprotease 9

SIRT-1:

Sirtuin-1

NFkB:

Nuclear factor kB

ER:

Endoplasmic reticulum

ELISA:

Enzyme-linked immunosorbent assay

SDS-PAGE:

Sodium dodecyl sulphate Poly acrylamide gel electrophoresis

NAD+ :

Nicotinamide adenine dinucleotide

qPCR:

Quantitative real-time PCR

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Acknowledgments

Financial assistance received from DST-SERB and KSCSTE is gratefully acknowledged.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Central University of Kerala, Nileshwar, Kasargod, Kerala, India

    Lincy Edatt, K. Haritha, T. V. Sruthi, P. Aswini & V. B. Sameer Kumar

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  1. Lincy Edatt
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  2. K. Haritha
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  3. T. V. Sruthi
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  4. P. Aswini
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  5. V. B. Sameer Kumar
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Correspondence to V. B. Sameer Kumar.

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Edatt, L., Haritha, K., Sruthi, T.V. et al. 2-Deoxy glucose regulate MMP-9 in a SIRT-1 dependent and NFkB independent mechanism. Mol Cell Biochem 423, 197–206 (2016). https://doi.org/10.1007/s11010-016-2837-4

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  • DOI: https://doi.org/10.1007/s11010-016-2837-4

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