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Depletion of PKM2 leads to impaired glycolysis and cell death in 2-demethoxy-2,3-ethylenediamino hypocrellin B-photoinduced A549 cells

Paper ID Volume ID Publish Year Pages File Format Full-Text
29404 44389 2014 8 PDF Available
Title
Depletion of PKM2 leads to impaired glycolysis and cell death in 2-demethoxy-2,3-ethylenediamino hypocrellin B-photoinduced A549 cells
Abstract

•EDAHB-PDT induces an early apoptosis in A549 cells.•EDAHB-PDT down-regulated PKM2 in A549 cells.•Ectopic over-expression of PKM2 attenuated photocytotoxicity of EDAHB.•Knockdown of PKM2 expression increased the photocytotoxicity of EDAHB.•Down-regulation of PKM2 by EDAHB-PDT modified the aerobic glycolysis.

2-Demethoxy-2,3-ethylenediamino hypocrellin B (EDAHB) is an efficient photosensitizer that mediates cancer cell apoptosis. In order to better understand the molecular mechanisms involved in its antitumour activity, we used proteomics technology to identify candidate targets in A549 cells using EDAHB-mediated photodynamic therapy (EDAHB-PDT). The protein profile changes between untreated and PDT-treated A549 cells were analysed using two-dimensional polyacrylamide gel electrophoresis (2-DE). Differentially expressed protein spots were identified using matrix-assisted laser desorption-time-of-flight (MALDI-TOF) mass spectrometry; and 15 differentially expressed proteins (over 2-fold, p < 0.05) were identified in PDT-treated A549 cells compared with untreated cells. Among them, the expression of pyruvate kinase M2 (PKM2), a key enzyme involved in glycolysis, was found to be significantly decreased in A549 cells following EDAHB-PDT. Transient ectopic over-expression of PKM2 attenuated death of EDAHB-PDT-treated A549 cells, whereas knockdown of PKM2 expression by RNA interference increased the photocytotoxicity of EDAHB. Moreover, a decrease in lactate production was detected in PDT-treated A549 cells. These observations suggest that PKM2 plays an important role in the antitumour action of EDAHB-PDT; thus, it may be a potential molecular target to increase the efficacy of PDT in cancer therapy.

Keywords
Photodynamic therapy (PDT); 2-Demethoxy-2,3-ethylenediamino hypocrellin B (EDAHB); A549 cells; Pyruvate kinase M2 (PKM2); Proteome
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Depletion of PKM2 leads to impaired glycolysis and cell death in 2-demethoxy-2,3-ethylenediamino hypocrellin B-photoinduced A549 cells
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Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Photochemistry and Photobiology B: Biology - Volume 134, 5 May 2014, Pages 1–8
Authors
, , , , , , ,
Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us