title: Arsenic trioxide induces autophagy and antitumor effects in Burkitt's lymphoma Raji cells.
abstract: Although it is generally acknowledged that auto-phagy plays an important role in tumorigenesis and therapy, studies of autophagy in different cell types and under different conditions have led to conflicting theories regarding the influence of autophagy on cell death. In the present study, we explored the role of autophagy and its underlying mechanism in the inhibitory effects of arsenic trioxide (As2O3) on Burkitt's lymphoma Raji cells. The results showed that As2O3 significantly inhibited the proliferation of Raji cells in a dose- and time-dependent manner, induced G2/M phase cell cycle arrest and apoptosis. Moreover, As2O3 also promoted the formation of autophagic vacuoles, as well as increased the degradation of autophagy substrate P62 protein, which was accompanied by an upregulation of Beclin-1 gene and a downregulation of Bcl-2 gene expression. 3-Methyladenine, an autophagy inhibitor, not only increased cell viability through inhibiting autophagic cell death and apoptosis, but also reversed the upregulation of Beclin-1 gene and the downregulation of Bcl-2 gene in the Raji cells induced by As2O3. These results may lead to a better understanding of the action of As2O3 and may provide evidence that autophagy plays an important role in the regulation of cell death. Therefore, regulation of autophagic activity may be a promising therapy for patients with Burkitt's lymphoma.
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
authors.forename: Cai-Li
authors.initials: CL
authors.lastname: Li
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
authors.forename: Hu-Lai
authors.initials: HL
authors.lastname: Wei
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
authors.forename: Bei
authors.initials: B
authors.lastname: Wang
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
authors.forename: Bei
authors.initials: B
authors.lastname: Xie
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
authors.forename: Lin-Lan
authors.initials: LL
authors.lastname: Fan
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
authors.forename: Lin-Jing
authors.initials: LJ
authors.lastname: Li
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1; D002051:Burkitt Lymphoma; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D004354:Drug Screening Assays, Antitumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D019254:Genes, bcl-2 / Q000187:drug effects; D006801:Humans; D008565:Membrane Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D010087:Oxides / Q000494:pharmacology*; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D001152:Arsenicals; C491997:BECN1 protein, human; D000071186:Beclin-1; D008565:Membrane Proteins; D010087:Oxides; C025946:3-methyladenine; D000225:Adenine; D000077237:Arsenic Trioxide