Alcohol induces cell proliferation via hypermethylation of ADHFE1 in colorectal cancer cells

Ji W. Moon, Soo K. Lee, Yong W. Lee, Jung O. Lee, Nami Kim, Hye J. Lee, Jung S. Seo, Jin Kim, Hyeon S. Kim, Sun Hwa Park

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)


Background: The hypermethylation of Alcohol dehydrogenase iron containing 1 (ADHFE1) was recently reported to be associated with colorectal cancer (CRC) differentiation. However, the effect of alcohol on ADHFE1 hypermethylation in CRC is still unclear.Methods: The methylation status and expression levels of ADHFE1 were investigated in primary tumor tissues and adjacent normal tissues of 73 patients with CRC, one normal colon cell line, and 4 CRC cell lines (HT-29, SW480, DLD-1, and LoVo) by quantitative methylation-specific polymerase chain reaction (QMSP) and real-time reverse transcription polymerase chain reaction (real time PCR), respectively. The effect of alcohol on the methylation status of ADHFE1 was analyzed in HT-29, SW480, DLD-1, and CCD18Co cells using QMSP, real-time PCR, immunoblot, and cell proliferation assay.Results: ADHFE1 was hypermethylated in 69 of 73 CRC tissues (95%) compared to adjacent normal tissues (p < 0.05). The mRNA expression of ADHFE1 was significantly reduced in CRC compared to adjacent normal tissues (p < 0.05) and its expression was decreased in the alcohol consumption group (p < 0.05). ADHFE1 was hypermethylated and its expression was decreased in 4 CRC cell lines compared with normal colon cell line. Alcohol induced hypermethylation of ADHFE1, decreased its expression, and stimulated cell proliferation of HT-29, SW480, and DLD-1cells.Conclusion: These results demonstrate that the promoter hypermethylation of ADHFE1 is frequently present in CRC and alcohol induces methylation-mediated down expression of ADHFE1 and proliferation of CRC cells.

Original languageEnglish
Article number377
JournalBMC Cancer
Issue number1
Publication statusPublished - 2014 May 28

Bibliographical note

Funding Information:
This study was supported by a Korea University Grant (K1132261) and the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (grant number: 2010–0024117).


  • ADHFE1
  • Alcohol
  • Colorectal cancer
  • Hypermethylation
  • Quantitative methylation-specific polymerase chain reaction

ASJC Scopus subject areas

  • Genetics
  • Oncology
  • Cancer Research


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