title: Apoptosis induced by adenosine involves endoplasmic reticulum stress             in EC109 cells.
abstract: Apoptosis plays a critical role in the development and homeostasis of multicellular             organisms, and endoplasmic reticulum stress (ERS) is one of the intrinsic apoptosis             pathways. Previous studies have shown that adenosine induces apoptosis in several             cancer cell lines. However, the molecular mechanism remains poorly understood.             In this study, we explored whether adenosine triggers apoptosis of EC109 esophageal             carcinoma (EC) cells by ERS. The MTT assay was used to determine cell proliferation;             cell cycle detection (FCM) and terminal deoxynucleotidyl transferase-mediated             dUTP nick end labeling (TUNEL) assay were performed to determine cell apoptosis.             The subcellular distribution and expression of the ERS-related proteins GRP78,             cleaved caspase-3, cleaved caspase-4, CHOP and NF-κB p65 were detected by western             blot techniques. NF-κB activation was measured by electrophoretic mobility shift             assay (EMSA). The MTT assay demonstrated that adenosine inhibited EC109 cell proliferation             in a dose- and time-dependent manner. FCM and TUNEL assay verified that adenosine             caused an apoptotic peak in cell cycle arrest and a higher percentage of apoptotic             cells. Western blot analysis confirmed that the expression of GRP78, cleaved caspase-4,             CHOP, NF-κB p65 and cleaved caspase-3 were upregulated in a dose-dependent manner             after adenosine treatment. EMSA revealed that adenosine activated NF-κB p65. This             is the first demonstration that adenosine inhibits cell proliferation, increases             GRP78 and NF-κB p65 expression and induces apoptosis by CHOP and caspase-4 pathways.             The ERS pathway is involved in adenosine-induced apoptosis in EC109 cells.
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital, Shantou University Medical College, Shantou 515041, PR China. lingfeiwu@21cn.com
authors.forename: Ling-Fei
authors.initials: LF
authors.lastname: Wu
authors.forename: Bi-Liu
authors.initials: BL
authors.lastname: Wei
authors.forename: Yi-Tian
authors.initials: YT
authors.lastname: Guo
authors.forename: Yan-Qing
authors.initials: YQ
authors.lastname: Ye
authors.forename: Guo-Ping
authors.initials: GP
authors.lastname: Li
authors.forename: Ze-Jin
authors.initials: ZJ
authors.lastname: Pu
authors.forename: Jia-Lin
authors.initials: JL
authors.lastname: Feng
mesh_terms: D000241:Adenosine / Q000378:metabolism*; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053471:Caspases, Initiator / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress; D004938:Esophageal Neoplasms / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D051742:Transcription Factor CHOP / Q000378:metabolism
chemical_list: C497249:DDIT3 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D016328:NF-kappa B; D051742:Transcription Factor CHOP; C093516:CASP4 protein, human; D053148:Caspase 3; D053471:Caspases, Initiator; D000241:Adenosine