title: 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.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, China. Electronic address: zhouzhixiang@bjut.edu.cn.
authors.forename: Zhixiang
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, China.
authors.forename: Yanghua
authors.initials: Y
authors.lastname: Liu
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, China.
authors.forename: Mengnan
authors.initials: M
authors.lastname: Qin
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Sheng
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wang
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, China.
authors.forename: Zelin
authors.initials: Z
authors.lastname: Li
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, China.
authors.forename: Rugang
authors.initials: R
authors.lastname: Zhong
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D015180:Electrophoresis, Gel, Two-Dimensional; D006019:Glycolysis / Q000187:drug effects*; D006801:Humans; D008027:Light; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010569:Perylene / Q000031:analogs & derivatives* / Q000633:toxicity; D017319:Photosensitizing Agents / Q000633:toxicity*; D020543:Proteome / Q000032:analysis / Q000378:metabolism; D011810:Quinoxalines / Q000633:toxicity*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013963:Thyroid Hormones / Q000235:genetics / Q000378:metabolism*; D000097810:Thyroid Hormone-Binding Proteins
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D010569:Perylene; D017319:Photosensitizing Agents; D020543:Proteome; D011810:Quinoxalines; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D013963:Thyroid Hormones; D000097810:Thyroid Hormone-Binding Proteins; C581200:2-demethoxy-2,3-ethylenediamino hypocrellin B
keywords: 2-Demethoxy-2,3-ethylenediamino hypocrellin B (EDAHB); A549 cells; Photodynamic therapy (PDT); Proteome; Pyruvate kinase M2 (PKM2)