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      Green tea polyphenol EGCG reverse cisplatin resistance of A549/DDP cell line through candidate genes demethylation.

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          Abstract

          Epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, has been extensively studied as a potential demethylating agent. Our hypothesis is that EGCG could resensitize non-small-cell lung cancer (NSCLC) cells to cisplatin (DDP) through candidate genes demethylation. The A549/DDP cell line was established by continuous exposure of A549 cells to increasing concentrations of DDP. MTT, colony formation assay, flow cytometric analysis, Hoechst staining, real time-PCR, quantitative methylation-specific PCR and in vivo experiments were performed in this study. EGCG+DDP treatment significantly caused proliferation inhibition, cell cycle arrest in G1 phase, increase of apoptosis in A549/DDP cells, along with inhibition of DNA methyltransferase (DNMT) activity and histone deacetylase (HDAC) activity, reversal of hypermethylated status and downregulated expression of GAS1, TIMP4, ICAM1 and WISP2 gene in A549/DDP cells. Furthermore, pre-treatment with EGCG followed by DDP caused significant tumor inhibition in vivo. Methylation levels of GAS1, TIMP4, ICAM1 and WISP2 were decreased and their expression levels were increased in EGCG-treatment groups, but only combinatorial treatment group caused growth inhibition. In conclusion, we identified EGCG pretreatment resensitized cells to DDP, along with the demethylation and restoration of expression of candidate genes.

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          Author and article information

          Journal
          Biomed. Pharmacother.
          Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
          Elsevier BV
          1950-6007
          0753-3322
          Feb 2015
          : 69
          Affiliations
          [1 ] Department of Medical Oncology, Xuzhou Central Hospital, Xuzhou Medical College, Xuzhou 221009, China.
          [2 ] Department of Medical Oncology, Xuzhou Central Hospital, Xuzhou Medical College, Xuzhou 221009, China. Electronic address: ss05181@189.cn.
          Article
          S0753-3322(14)00211-X
          10.1016/j.biopha.2014.12.016
          25661371
          e2c981be-3cb4-4511-bc2d-867ea3acdcad
          History

          Epigallocatechin-3-gallate,Cisplatin,Lung cancer,Methylation

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