Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
July-2016 Volume 12 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
July-2016 Volume 12 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Delineating the effect of demethylating agent 5-aza-2'-deoxycytidine on human Caco-2 colonic carcinoma cells

  • Authors:
    • Xiumei Li
    • Bingzhao Qin
    • Bo Liu
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology, Xiangyang Hospital Affiliated to Hubei University of Medicine, Xiangyang, Hubei 441000, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 139-143
    |
    Published online on: May 9, 2016
       https://doi.org/10.3892/ol.2016.4551
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Aberrant epigenetic changes are known to contribute to various phases of tumor development. The gene function loss caused by aberrant methylation is analogous to genetic mutations. Unlike genetic mutations, epigenetic alterations can be reversed. 5-Aza-2'-deoxycytidine (5-aza-CdR) has been approved by the Food and Drug Administration for the treatment of certain types of cancer, such as MDS and leukemia. The aim of the present study was to determine whether 5-aza-CdR has the potential to be used in the treatment of colon cancer using a human Caco‑2 colonic carcinoma cell line. The effect of 5‑aza‑CdR on cell proliferation, cell cycle, apoptosis and reversal of aberrant methylation of the Ras association domain family 1A (RASSF1A) gene was also examined. The 5‑aza‑CdR was prepared at different concentrations in sterile tri‑distilled water at 0.4, 1.6, 6.4, 25.6  and 102.4 µmol/l and employed to treat the human Caco‑2 colonic carcinoma cells. An MTT assay was used to detect the effect of 5‑aza‑CdR on cell proliferation. Flow cytometry was used to examine the cell cycle and apoptosis. The RASSF1A mRNA transcript level was examined by reverse transcription-polymerase chain reaction. The results showed that 5‑aza‑CdR inhibited the proliferation of Caco‑2 cells in a time‑ and concentration‑dependent manner (p<0.01). The 5‑aza‑CdR treatment affected the cell cycle and caused accumulation of cells in the G0/G1 phase and this effect was concentration‑dependent (p<0.05). 5‑aza‑CdR treatment caused an increase in the number of cells undergoing apoptosis and reactivated the RASSF1A tumor suppressor gene that was silenced by hypermethylation in Caco-2 cells. In conclusion, 5‑aza‑CdR inhibited growth and promoted apoptosis in Caco‑2 cells by upregulating the epigenetically silenced tumor suppressor RASSF1A gene.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Fandy TE: Development of DNA methyltransferase inhibitors for the treatment of neoplastic diseases. Curr Med Chem. 16:2075–2085. 2009. View Article : Google Scholar : PubMed/NCBI

2 

Zhang Y, Ng HH, Erdjument-Bromage H, Tempst P, Bird A and Reinberg D: Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation. Genes Dev. 13:1924–1935. 1999. View Article : Google Scholar : PubMed/NCBI

3 

Prokhortchouk A, Hendrich B, Jørgensen H, Ruzov A, Wilm M, Georgiev G, Bird A and Prokhortchouk E: The p120 catenin partner Kaiso is a DNA methylation-dependent transcriptional repressor. Genes Dev. 15:1613–1618. 2001. View Article : Google Scholar : PubMed/NCBI

4 

Bird AP: The relationship of DNA methylation to cancer. Cancer Surv. 28:87–101. 1996.PubMed/NCBI

5 

Bird A: DNA methylation de novo. Science. 286:2287–2288. 1999. View Article : Google Scholar : PubMed/NCBI

6 

Dammann R, Li C, Yoon JH, Chin PL, Bates S and Pfeifer GP: Epigenetic inactivation of a RAS association domain family protein from the lung tumour suppressor locus 3p21.3. Nat Genet. 25:315–319. 2000. View Article : Google Scholar : PubMed/NCBI

7 

Dammann R, Takahashi T and Pfeifer GP: The CpG island of the novel tumor suppressor gene RASSF1A is intensely methylated in primary small cell lung carcinomas. Oncogene. 20:3563–3567. 2001. View Article : Google Scholar : PubMed/NCBI

8 

Bartling B, Hoffmann J, Holtz J, Schulz R, Heusch G and Darmer D: Quantification of cardioprotective gene expression in porcine short-term hibernating myocardium. J Mol Cell Cardiol. 31:147–158. 1999. View Article : Google Scholar : PubMed/NCBI

9 

Burbee DG, Forgacs E, Zöchbauer-Müller S, Shivakumar L, Fong K, Gao B, Randle D, Kondo M, Virmani A, Bader S, et al: Epigenetic inactivation of RASSF1A in lung and breast cancers and malignant phenotype suppression. J Natl Cancer Inst. 93:691–699. 2001. View Article : Google Scholar : PubMed/NCBI

10 

Piekarz RL and Bates SE: Epigenetic modifiers: basic understanding and clinical development. Clin Cancer Res. 15:3918–3926. 2009. View Article : Google Scholar : PubMed/NCBI

11 

Wijermans P, Lubbert M, Verhoef G, Bosly A, Ravoet C, Andre M and Ferrant A: Low-dose 5-Aza-2′-deoxycytidine, a DNA hypomethylation agent for the treatment of high-risk myelodyspastic syndrome: a multicenter phase II study in elderly patients. J Clin Oncol. 18:956–960. 2000.PubMed/NCBI

12 

Xhu XJ and Dai DQ: Epigenetics and gastrointestinal cancer. Chin J Digest. 14:3215–3256. 2006.

13 

Tomita H, Hirata A, Yamada Y, Hata K, Oyama T, Mori H, Yamashita S, Ushijima T and Hara A: Suppressive effect of global DNA hypomethylation on gastrc carcinogenesis. Carcinogenesis. 31:1627–1633. 2010. View Article : Google Scholar : PubMed/NCBI

14 

Zöchbauer-Müller S, Fong KM, Virmani AK, Geradts J, Gazdar AF and Minna JD: Aberrant promoter methylation of multiple genes in non-small cell lung cancers. Cancer Res. 61:249–255. 2001.PubMed/NCBI

15 

Daskalakis M, Nguyen TT, Nguyen C, Guldberg P, Köhler G, Wijermans P, Jones PA and Lübbert M: Demethylation of a hypermethylated P15/INK4B gene in patients with myelodysplastic syndrome by 5-Aza-2′-deoxycytidine (decitabine) treatment. Blood. 100:2957–2964. 2002. View Article : Google Scholar : PubMed/NCBI

16 

Bae SI, Lee HS, Kim SH and Kim WH: Inactivation of O6-methylguanine-DNA methyltransferase by promoter CpG island hypermethylation in gastric cancers. Br J Cancer. 86:1888–1892. 2002. View Article : Google Scholar : PubMed/NCBI

17 

Esteller M, Corn PG, Baylin SB and Herman JG: A gene hypermethylation profile of human cancer. Cancer Res. 61:3225–3229. 2001.PubMed/NCBI

18 

Lübbert M, Tobler A and Daskalakis M: Cytosine demethylation of the proteinase-3/myeloblastin primary granule protease gene during phagocyte development. Leukemia. 13:1420–1427. 1999. View Article : Google Scholar : PubMed/NCBI

19 

Kim SH, Bae SI, Lee HS and Kim WH: Alteration of O6-methylguanine-DNA methyltransferase in colorectal neoplasms in sporadic and familial adenomatous polyposis patients. Mol Carcinog. 37:32–38. 2003. View Article : Google Scholar : PubMed/NCBI

20 

Bender CM, Pao MM and Jones PA: Inhibition of DNA methylation by 5-aza-2′-deoxycytidine suppresses the growth of human tumor cell lines. Cancer Res. 58:95–101. 1998.PubMed/NCBI

21 

Gonzalgo ML, Hayashida T, Bender CM, Pao MM, Tsai YC, Gonzales FA, Nguyen HD, Nguyen TT and Jones PA: The role of DNA methylation in expression of the p19/p16 locus in human bladder cancer cell lines. Cancer Res. 58:1245–1252. 1998.PubMed/NCBI

22 

Xiong Z, Wu AH, Bender CM, Tsao JL, Blake C, Shibata D, Jones PA, Yu MC, Ross RK and Laird PW: Mismatch repair deficiency and CpG island hypermethylation in sporadic colon adenocarcinomas. Cancer Epidemiol Biomarkers Prev. 10:799–803. 2001.PubMed/NCBI

23 

Dammann R, Schagdarsurengin U, Strunnikova M, Rastetter M, Seidel C, Liu L, Tommasi S and Pfeifer GP: Epigenetic inactivation of the Ras-association domain family 1 (RASSF1A) gene and its function in human carcinogenesis. Histol Histopathol. 18:665–677. 2003.PubMed/NCBI

24 

Liu L, Tommasi S, Lee DH, Dammann R and Pfeifer GP: Control of microtubule stability by the RASSF1A tumor suppressor. Oncogene. 22:8125–8136. 2003. View Article : Google Scholar : PubMed/NCBI

25 

Strunnikova M, Schagdarsurengin U, Kehlen A, Garbe JC, Stampfer MR and Dammann R: Chromatin inactivation precedes de novo DNA methylation during the progressive epigenetic silencing of the RASSF1A promoter. Mol Cell Biol. 25:3923–3933. 2005. View Article : Google Scholar : PubMed/NCBI

26 

Chow LS, Lo KW, Kwong J, To KF, Tsang KS, Lam CW, Dammann R and Huang DP: RASSF1A is a target tumor suppressor from 3p21.3 in nasopharyngeal carcinoma. Int J Cancer. 109:839–847. 2004. View Article : Google Scholar : PubMed/NCBI

27 

Tommasi S, Dammann R, Zhang Z, Wang Y, Liu L, Tsark WM, Wilczynski SP, Li J, You M and Pfeifer GP: Tumor susceptibility of Rassf1a knockout mice. Cancer Res. 65:92–98. 2005.PubMed/NCBI

28 

Lee S, Hwang KS, Lee HJ, Kim JS and Kang GH: Aberrant CpG island hypermethylation of multiple genes in colorectal neoplasia. Lab Invest. 87:884–893. 2004. View Article : Google Scholar

29 

Kang GH, Lee HJ, Hwang KS, Lee S, Kim JH and Kim JS: Aberrant CpG island hypermethylation of chronic gastritis, in relation to aging, gender, intestinal metaplasia, and chronic inflammation. Am J Pathol. 163:1551–1556. 2003. View Article : Google Scholar : PubMed/NCBI

30 

Kuroki T, Trapasso F, Yendamuri S, Matsuyama A, Alder H, Mori M and Croce CM: Allele loss and promoter hypermethylation of VHL, RAR-beta, RASSF1A, and FHIT tumor suppressor genes on chromosome 3p in esophageal squamous cell carcinoma. Cancer Res. 63:3724–3728. 2003.PubMed/NCBI

31 

Kuroki T, Trapasso F, Yendamuri S, Matsuyama A, Alder H, Mori M and Croce CM: Promoter hypermethylation of RASSF1A in esophageal squamous cell carcinoma. Clin Cancer Res. 9:1441–1445. 2003.PubMed/NCBI

32 

Byun DS, Lee MG, Chae KS, Ryu BG and Chi SG: Frequent epigenetic inactivation of RASSF1A by aberrant promoter hypermethylation in human gastric adenocarcinoma. Cancer Res. 61:7034–7038. 2001.PubMed/NCBI

33 

Lee MG, Kim HY, Byun DS, Lee SJ, Lee CH, Kim JI, Chang SG and Chi SG: Frequent epigenetic inactivation of RASSF1A in human bladder carcinoma. Cancer Res. 61:6688–6692. 2001.PubMed/NCBI

34 

Chan MW, Chan LW, Tang NL, Lo KW, Tong JH, Chan AW, Cheung HY, Wong WS, Chan PS, Lai FM, et al: Frequent hypermethylation of promoter region of RASSF1A in tumor tissues and voided urine of urinary bladder cancer patients. Int J Cancer. 104:611–616. 2003. View Article : Google Scholar : PubMed/NCBI

35 

Müller HM, Widschwendter A, Fiegl H, Ivarsson L, Goebel G, Perkmann E, Marth C and Widschwendter M: DNA methylation in serum of breast cancer patients: an independent prognostic marker. Cancer Res. 63:7641–7645. 2003.PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Li X, Qin B and Liu B: Delineating the effect of demethylating agent 5-aza-2'-deoxycytidine on human Caco-2 colonic carcinoma cells. Oncol Lett 12: 139-143, 2016.
APA
Li, X., Qin, B., & Liu, B. (2016). Delineating the effect of demethylating agent 5-aza-2'-deoxycytidine on human Caco-2 colonic carcinoma cells. Oncology Letters, 12, 139-143. https://doi.org/10.3892/ol.2016.4551
MLA
Li, X., Qin, B., Liu, B."Delineating the effect of demethylating agent 5-aza-2'-deoxycytidine on human Caco-2 colonic carcinoma cells". Oncology Letters 12.1 (2016): 139-143.
Chicago
Li, X., Qin, B., Liu, B."Delineating the effect of demethylating agent 5-aza-2'-deoxycytidine on human Caco-2 colonic carcinoma cells". Oncology Letters 12, no. 1 (2016): 139-143. https://doi.org/10.3892/ol.2016.4551
Copy and paste a formatted citation
x
Spandidos Publications style
Li X, Qin B and Liu B: Delineating the effect of demethylating agent 5-aza-2'-deoxycytidine on human Caco-2 colonic carcinoma cells. Oncol Lett 12: 139-143, 2016.
APA
Li, X., Qin, B., & Liu, B. (2016). Delineating the effect of demethylating agent 5-aza-2'-deoxycytidine on human Caco-2 colonic carcinoma cells. Oncology Letters, 12, 139-143. https://doi.org/10.3892/ol.2016.4551
MLA
Li, X., Qin, B., Liu, B."Delineating the effect of demethylating agent 5-aza-2'-deoxycytidine on human Caco-2 colonic carcinoma cells". Oncology Letters 12.1 (2016): 139-143.
Chicago
Li, X., Qin, B., Liu, B."Delineating the effect of demethylating agent 5-aza-2'-deoxycytidine on human Caco-2 colonic carcinoma cells". Oncology Letters 12, no. 1 (2016): 139-143. https://doi.org/10.3892/ol.2016.4551
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team