title: Transcriptomic and functional pathways analysis of ascorbate-induced cytotoxicity and resistance of Burkitt lymphoma.
abstract: Ascorbate is a pro-oxidant that generates hydrogen peroxide-dependent cytotoxity in cancer cells without adversely affecting normal cells. To determine the mechanistic basis for this phenotype, we selected Burkitt lymphoma cells resistant to ascorbate (JLPR cells) and their ascorbate-sensitive parental cells (JLPS cells). Compared with JLPS cells, the increased glucose uptake in JLPR cells (with upregulated glucose transporters, increased antioxidant enzyme activity, and altered cell cycling) conferred ascorbate-induced cytotoxicity and resistance. Transcriptomic profiles and function pathway analysis identified differentially expressed gene signatures for JLPR cells and JLPS cells, which differential expression levels of five genes (ATF5, CD79B, MHC, Myosin, and SAP18) in ascorbate-resistant cells were related to phosphoinositide 3 kinase, cdc42, DNA methylation and transcriptional repression, polyamine regulation, and integrin-linked kinase signaling pathways. These results suggested that coordinated changes occurred in JLPR cells to enable their survival when exposed to the cytotoxic pro-oxidant stress elicited by pharmacologic ascorbate treatment.
authors: Scientific Research Center, Shanghai Public Health Clinical Center, Jinshan District, Shanghai 201508, China.
authors: Zenglin
authors: Z
authors: Pei
authors: Scientific Research Center, Shanghai Public Health Clinical Center, Jinshan District, Shanghai 201508, China.
authors: Xuan
authors: X
authors: Zhang
authors: Scientific Research Center, Shanghai Public Health Clinical Center, Jinshan District, Shanghai 201508, China.
authors: Chunxia
authors: C
authors: Ji
authors: Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China.
authors: Song-Mei
authors: SM
authors: Liu
authors: Scientific Research Center, Shanghai Public Health Clinical Center, Jinshan District, Shanghai 201508, China.
authors: Jin
authors: J
authors: Wang
mesh_terms: D051696:Activating Transcription Factors / Q000378:metabolism; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001205:Ascorbic Acid / Q000494:pharmacology*; D002051:Burkitt Lymphoma / Q000188:drug therapy* / Q000378:metabolism*; D051925:CD79 Antigens / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D056970:Co-Repressor Proteins; D019008:Drug Resistance, Neoplasm; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008285:Major Histocompatibility Complex; D009218:Myosins / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D016601:RNA-Binding Proteins; D017382:Reactive Oxygen Species; D015398:Signal Transduction / Q000187:drug effects; D059467:Transcriptome
chemical_list: D051696:Activating Transcription Factors; D000975:Antioxidants; D001205:Ascorbic Acid; D051925:CD79 Antigens; D002352:Carrier Proteins; D056970:Co-Repressor Proteins; D006861:Hydrogen Peroxide; D009218:Myosins; D019869:Phosphatidylinositol 3-Kinases; D016601:RNA-Binding Proteins; D017382:Reactive Oxygen Species; C507532:ATF5 protein, human; C498650:SAP18 protein, human
keywords: Burkitt lymphoma cells; ascorbate; drug resistance; pathway analysis; transcriptomic profiles