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

Abstract

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.

• Authors: Zhixiang Zhou, Yanghua Liu, Mengnan Qin, Wang Sheng, Xiaoli Wang, Zelin Li, Rugang Zhong
• Journal: Journal of photochemistry and photobiology. B, Biology (J Photochem Photobiol B) Vol. 134 Pg. 1-8 (May 05 2014) ISSN: 1873-2682 [Electronic] Switzerland
• PMID: 24792468 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• 2-demethoxy-2,3-ethylenediamino hypocrellin B
• Carrier Proteins
• Membrane Proteins
• Photosensitizing Agents
• Proteome
• Quinoxalines
• RNA, Messenger
• RNA, Small Interfering
• Thyroid Hormones
• thyroid hormone-binding proteins
• Perylene

Topics

• Apoptosis (drug effects, radiation effects)
• Carrier Proteins (antagonists & inhibitors, genetics, metabolism)
• Cell Line, Tumor
• Electrophoresis, Gel, Two-Dimensional
• Glycolysis (drug effects)
• Humans
• Light
• Membrane Proteins (antagonists & inhibitors, genetics, metabolism)
• Perylene (analogs & derivatives, toxicity)
• Photosensitizing Agents (toxicity)
• Proteome (analysis, metabolism)
• Quinoxalines (toxicity)
• RNA Interference
• RNA, Messenger (metabolism)
• RNA, Small Interfering (metabolism)
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
• Thyroid Hormones (genetics, metabolism)