title: Combination treatment with oxaliplatin and mangiferin causes increased apoptosis and downregulation of NFκB in cancer cell lines.
abstract: Mangiferin-mediated down-regulation of NFκB showed potential for chemotherapeutic agent-mediated cell death, suggesting a role in combination therapy for cancer. In this study the combined mechanism of the anticancer action of oxaliplatin and mangiferin was investigated. MTT dose response curves, trypan blue staining, caspase 3 assays as well as DNA cell cycle analyses were performed on HeLa, HT29 and MCF7 cancer cell lines, with and without the addition of 10 µg/ml mangiferin. Mitochondrial membrane potential, DNA fragmentation, resistance induction studies and NFκB assays were performed on HT29 cells only. Addition of 10 µg/ml mangiferin reduced oxaliplatin IC(50) values in HT29 (3.4 fold) and HeLa (1.7 fold) cells in the MTT assay while reducing trypan blue staining. This was accompanied by increased caspase 3 activation and DNA fragmentation and a delay in the S-phase of the cell cycle. Mitochondrial membrane permeabilization was not enhanced in the combination treatment. Mangiferin was shown to cause a reduction of NF-κB activation in HT29 cells rendered resistant to oxaliplatin. The present study indicates that mangiferin in combination with oxaliplatin favours apoptotic cell death and thereby improves the efficacy of oxaliplatin in vitro. In addition, combination therapy with mangiferin may also counteract the development of resistance in cancer cell lines.
authors.affiliation: Department of Biochemistry and Microbiology, Nelson Mandela Metropolitan University, Port Elizabeth, South Africa.
authors.forename: D
authors.initials: D
authors.lastname: du Plessis-Stoman
authors.forename: Jgh
authors.initials: J
authors.lastname: du Preez
authors.forename: M
authors.initials: M
authors.lastname: van de Venter
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000187:drug effects; D045744:Cell Line, Tumor; D053938:DNA Fragmentation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm; D004359:Drug Therapy, Combination; D016193:G1 Phase / Q000187:drug effects; D019073:HT29 Cells; D006367:HeLa Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism; D009944:Organoplatinum Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D000077150:Oxaliplatin; D016196:S Phase / Q000187:drug effects; D044004:Xanthones / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D016328:NF-kappa B; D009944:Organoplatinum Compounds; D044004:Xanthones; D000077150:Oxaliplatin; C013592:mangiferin; D053148:Caspase 3