TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000257430
  • Gene Name:APC
  • mRNA database:Ensembl
  • mRNA expression :up-regulated
  • mRNA Method:RT-PCR
  • mRNA Pathway:NA
  • Evidence:validated
  • (mRNA-drug)

Drug basic information

  • Drug ID:NA
  • Drug Name:Trichosanthin
  • Drug Method:up-regulated the gene expression

Disease basic infommation

  • Disease:cervical cancer
  • Tissue:cell lines (HeLa ,CaSki )

Other information

  • Title:Trichosanthin inhibits DNA methyltransferase and restores methylation-silenced gene expression in human cervical cancer cells
  • Journal:Mol Med Rep
  • Published:2012
  • PubMed ID:22825485
  • Abstract:Epigenetic silencing of tumor suppressor genes is a well-established oncogenic process and the reactivation of tumor suppressor genes that have been silenced by promoter methylation is an attractive molecular target for cancer therapy. In this study, we investigated the demethylation activity of trichosanthin (TCS, the main bioactive component isolated from a Chinese medicinal herb) and its possible mechanism of action in cervical cancer cell lines. HeLa human cervical adenocarcinoma and CaSki human cervical squamous carcinoma cells were treated with various concentrations (0, 20, 40 and 80 碌g/ml) of TCS for 48 h and the mRNA and protein expression levels of the tumor suppressor genes adenomatous polyposis coli (APC) and tumor suppressor in lung cancer 1 (TSLC1) were detected using reverse transcription (RT)-PCR and western blotting, respectively. We analyzed the methylation status of APC and TSLC1 using methylation-speci铿乧 PCR (MSP). The expression levels and enzyme activity of DNA methyltransferase 1 (DNMT1) were also examined. The mRNA and protein expression levels of APC and TSLC1 were increased following treatment with various concentrations (0, 20, 40 and 80 碌g/ml) of TCS for 48 h. The expression of the APC gene increased 2.55卤0.29-, 3.44卤0.31- and 4.36卤0.14-fold, respectively. The expression of the TSLC1 gene increased 2.28卤0.15-, 4.23卤0.88- and 6.09卤0.23-fold, respectively. MSP detection showed that TCS induced demethylation in HeLa and CaSki cells and that this demethylation activity was accompanied by the decreased expression of DNMT1 and reduced DNMT1 enzyme activity. Our experimental results demonstrate for the first time that TCS is capable of restoring the expression of methylation-silenced tumor suppressor genes and is potentially useful as a demethylation agent for the clinical treatment of human cervical cancer.
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