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.