Melatonin-induced methylation of the ABCG2/BCRP promoter as a novel mechanism to overcome multidrug resistance in brain tumour stem cells
作者： V Martín , Ana María Sanchez-Sanchez , F Herrera , Candelaria Gomez-Manzano , J Fueyo
DOI: 10.1038/BJC.2013.188
关键词:
摘要: Current evidence indicates that a stem cell-like sub-population within malignant glioblastomas, overexpress members of the adenosine triphosphate-binding cassette (ABC) family transporters, is responsible for multidrug resistance and tumour relapse. Eradication brain cell (BTSC) compartment therefore essential to achieve stable long-lasting remission. Melatonin actions were analysed by viability assays, flow cytometry, quantitative PCR mRNA expression, western blot protein expression qualitative promoter methylation methods. Combinations melatonin chemotherapeutic drugs (including temozolomide, current treatment gliomas) have synergistic toxic effect on BTSCs A172 glioma cells. This correlated with downregulation function ABC transporter ABCG2/BCRP. increased levels ABCG2/BCRP effects prevented preincubation DNA methyltransferase inhibitor. Our results point out possible relationship between drugs. could be promising candidate overcome in thus improve efficiency therapies.
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