title: Valproic Acid Enhances the Anti-tumor Effect of (-)-gossypol to Burkitt Lymphoma Namalwa Cells.
abstract: Burkitt lymphoma is a highly aggressive B-cell neoplasm. New therapeutic methods are needed to overcome the adverse effect of intensive chemotherapy regimens. Valproic acid and (-)-gossypol are two kinds of chemical compounds used as new anti-tumor drugs in recent years. To investigate the anti-tumor effect of valproic acid and (-)-gossypol, Burkitt lymphoma Namalwa cells were cultured and treated with valproic acid and (-)-gossypol at different concentrations. The proliferation of Namalwa cells was dramatically suppressed after the combination treatment with 2 mmol/L valproic acid and 5 μmol/L (-)-gossypol. The combined treatment also enhanced intrinsic apoptosis by down-regulating anti-apoptotic protein Mcl-1. Moreover, the autophagy flux significantly increased in Namalwa cells after combined treatment. However, the enhanced autophagy showed little effect on cell survival with present regimen. The results confirmed that combination of valproic acid and (-)-gossypol had synergistic anti-tumor effect to Burkitt lymphoma Namalwa cells. The related mechanisms might include the down-regulation of anti-apoptotic protein Mcl-1 and avianized pro-survival role of autophagy.
authors.affiliation: Department of Hematology, Xinqiao Hospital, The Third Military Medical University, Chongqing 400037, China; Department of Hematology-oncology, Chongqing Cancer Institute/Hospital, Chongqing 400030, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, The Third Military Medical University, Chongqing 400038, China.
authors.forename: Zhen Hong
authors.initials: ZH
authors.lastname: Ni
authors.affiliation: Department of Hematology, Xinqiao Hospital, The Third Military Medical University, Chongqing 400037, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Hematology, Xinqiao Hospital, The Third Military Medical University, Chongqing 400037, China.
authors.forename: Xing Hua
authors.initials: XH
authors.lastname: Chen
authors.affiliation: Institute of Toxicology, School of Preventive Medicine, The Third Military Medical University, Chongqing 400038, China.
authors.forename: Zhong Min
authors.initials: ZM
authors.lastname: Zou
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002051:Burkitt Lymphoma / Q000188:drug therapy*; D045744:Cell Line, Tumor; D003272:Contraceptive Agents, Male / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006072:Gossypol / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D014635:Valproic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D003272:Contraceptive Agents, Male; D004791:Enzyme Inhibitors; D014635:Valproic Acid; D006072:Gossypol