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
International Journal of Molecular Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1107-3756 Online ISSN: 1791-244X
Journal Cover
October-2016 Volume 38 Issue 4

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
October-2016 Volume 38 Issue 4

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

Epigallocatechin-3-gallate prevents oxidative stress-induced cellular senescence in human mesenchymal stem cells via Nrf2

  • Authors:
    • Joo-Hyun Shin
    • Hyo-Jin Jeon
    • Jihye Park
    • Mi-Sook Chang
  • View Affiliations / Copyright

    Affiliations: Laboratory of Stem Cell and Neurobiology, Department of Oral Anatomy, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 03080, Republic of Korea
    Copyright: © Shin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1075-1082
    |
    Published online on: August 1, 2016
       https://doi.org/10.3892/ijmm.2016.2694
  • 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

Human mesenchymal stem cells (hMSCs) have great therapeutic potential due to their high plasticity, immune privileged status and ease of preparation, as well as a lack of ethical barriers to their use. However, their ultimate usefulness is limited by cellular senescence occurring secondary to increased cellular levels of reactive oxygen species (ROS) during their propagation in culture. The underlying molecular mechanisms responsible for this process in hMSCs remain unclear. An antioxidant polyphenol epigallocatechin-3-gallate (EGCG) found in green tea, is known to activate nuclear factor-erythroid 2-related factor 2 (Nrf2), a master transcriptional regulator of antioxidant genes. Herein, we examined the EGCG-mediated antioxidant mechanism in hMSCs exposed to ROS which involves Nrf2 activation. The H2O2-exposed hMSCs showed cellular senescence with significantly increased protein levels of acetyl-p53 and p21 in comparison with the untreated hMSCs, and these effects were prevented by pre-treatment with EGCG. By contrast, in Nrf2-knockdown hMSCs, EGCG lost its antioxidant effect, exhibiting high levels of acetyl-p53 and p21 following EGCG pre-treatment and H2O2 exposure. This indicates that Nrf2 and p53/p21 may be involved in the anti‑senescent effect of EGCG in hMSCs. Taken together, these findings indicate the important role of EGCG in preventing oxidative stress-induced cellular senescence in hMSCs through Nrf2 activation, which has applications for the massive production of more suitable hMSCs for cell-based therapy.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Pittenger MF1, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S and Marshak DR: Multilineage potential of adult human mesenchymal stem cells. Science. 284:143–147. 1999. View Article : Google Scholar : PubMed/NCBI

2 

Sherman LS, Munoz J, Patel SA, Dave MA, Paige I and Rameshwar P: Moving from the laboratory bench to patients' bedside: considerations for effective therapy with stem cells. Clin Transl Sci. 4:380–386. 2011. View Article : Google Scholar : PubMed/NCBI

3 

Kuilman T, Michaloglou C, Mooi WJ and Peeper DS: The essence of senescence. Genes Dev. 24:2463–2479. 2010. View Article : Google Scholar : PubMed/NCBI

4 

López-Otín C, Blasco MA, Partridge L, Serrano M and Kroemer G: The hallmarks of aging. Cell. 153:1194–1217. 2013. View Article : Google Scholar : PubMed/NCBI

5 

Oh J, Lee YD and Wagers AJ: Stem cell aging: mechanisms, regulators and therapeutic opportunities. Nat Med. 20:870–880. 2014. View Article : Google Scholar : PubMed/NCBI

6 

Brandl A, Meyer M, Bechmann V, Nerlich M and Angele P: Oxidative stress induces senescence in human mesenchymal stem cells. Exp Cell Res. 317:1541–1547. 2011. View Article : Google Scholar : PubMed/NCBI

7 

Campisi J and d'Adda di Fagagna F: Cellular senescence: when bad things happen to good cells. Nat Rev Mol Cell Biol. 8:729–740. 2007. View Article : Google Scholar : PubMed/NCBI

8 

Kume S, Haneda M, Kanasaki K, Sugimoto T, Araki S, Isono M, Isshiki K, Uzu T, Kashiwagi A and Koya D: Silent information regulator 2 (SIRT1) attenuates oxidative stress-induced mesangial cell apoptosis via p53 deacetylation. Free Radic Biol Med. 40:2175–2182. 2006. View Article : Google Scholar : PubMed/NCBI

9 

Langley E, Pearson M, Faretta M, Bauer UM, Frye RA, Minucci S, Pelicci PG and Kouzarides T: Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence. EMBO J. 21:2383–2396. 2002. View Article : Google Scholar : PubMed/NCBI

10 

Luo J, Nikolaev AY, Imai S, Chen D, Su F, Shiloh A, Guarente L and Gu W: Negative control of p53 by Sir2α promotes cell survival under stress. Cell. 107:137–148. 2001. View Article : Google Scholar : PubMed/NCBI

11 

Vaziri H, Dessain SK, Ng Eaton E, Imai SI, Frye RA, Pandita TK, Guarente L and Weinberg RA: hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase. Cell. 107:149–159. 2001. View Article : Google Scholar : PubMed/NCBI

12 

Han DW, Lee MH, Kim B, Lee JJ, Hyon SH and Park JC: Preventive effects of epigallocatechin-3-O-gallate against replicative senescence associated with p53 acetylation in human dermal fibroblasts. Oxid Med Cell Longev. 2012:8506842012. View Article : Google Scholar : PubMed/NCBI

13 

Anderson RF, Fisher LJ, Hara Y, Harris T, Mak WB, Melton LD and Packer JE: Green tea catechins partially protect DNA from (.)OH radical-induced strand breaks and base damage through fast chemical repair of DNA radicals. Carcinogenesis. 22:1189–1193. 2001. View Article : Google Scholar : PubMed/NCBI

14 

Chow HH, Cai Y, Alberts DS, Hakim I, Dorr R, Shahi F, Crowell JA, Yang CS and Hara Y: Phase I pharmacokinetic study of tea polyphenols following single-dose administration of epigallocatechin gallate and polyphenon E. Cancer Epidemiol Biomarkers Prev. 10:53–58. 2001.PubMed/NCBI

15 

Higdon JV and Frei B: Tea catechins and polyphenols: health effects, metabolism, and antioxidant functions. Crit Rev Food Sci Nutr. 43:89–143. 2003. View Article : Google Scholar : PubMed/NCBI

16 

Yagi H, Tan J and Tuan RS: Polyphenols suppress hydrogen peroxide-induced oxidative stress in human bone-marrow derived mesenchymal stem cells. J Cell Biochem. 114:1163–1173. 2013. View Article : Google Scholar

17 

Surh YJ, Kundu JK, Na HK and Lee JS: Redox-sensitive transcription factors as prime targets for chemoprevention with anti-inflammatory and antioxidative phytochemicals. J Nutr. 135(Suppl 12): 2993S–3001S. 2005.PubMed/NCBI

18 

Hayes JD and McMahon M: NRF2 and KEAP1 mutations: permanent activation of an adaptive response in cancer. Trends Biochem Sci. 34:176–188. 2009. View Article : Google Scholar : PubMed/NCBI

19 

Itoh K, Wakabayashi N, Katoh Y, Ishii T, Igarashi K, Engel JD and Yamamoto M: Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain. Genes Dev. 13:76–86. 1999. View Article : Google Scholar : PubMed/NCBI

20 

Nguyen T, Nioi P and Pickett CB: The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress. J Biol Chem. 284:13291–13295. 2009. View Article : Google Scholar : PubMed/NCBI

21 

Burova E, Borodkina A, Shatrova A and Nikolsky N: Sublethal oxidative stress induces the premature senescence of human mesenchymal stem cells derived from endometrium. Oxid Med Cell Longev. 2013:4749312013. View Article : Google Scholar : PubMed/NCBI

22 

Dinkova-Kostova AT, Holtzclaw WD and Wakabayashi N: Keap1, the sensor for electrophiles and oxidants that regulates the phase 2 response, is a zinc metalloprotein. Biochemistry. 44:6889–6899. 2005. View Article : Google Scholar : PubMed/NCBI

23 

Bond J, Haughton M, Blaydes J, Gire V, Wynford-Thomas D and Wyllie F: Evidence that transcriptional activation by p53 plays a direct role in the induction of cellular senescence. Oncogene. 13:2097–2104. 1996.PubMed/NCBI

24 

Luo J, Li M, Tang Y, Laszkowska M, Roeder RG and Gu W: Acetylation of p53 augments its site-specific DNA binding both in vitro and in vivo. Proc Natl Acad Sci USA. 101:2259–2264. 2004. View Article : Google Scholar : PubMed/NCBI

25 

el-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, Lin D, Mercer WE, Kinzler KW and Vogelstein B: WAF1, a potential mediator of p53 tumor suppression. Cell. 75:817–825. 1993. View Article : Google Scholar : PubMed/NCBI

26 

Harper JW, Adami GR, Wei N, Keyomarsi K and Elledge SJ: The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Cell. 75:805–816. 1993. View Article : Google Scholar : PubMed/NCBI

27 

Brown JP, Wei W and Sedivy JM: Bypass of senescence after disruption of p21CIP1/WAF1 gene in normal diploid human fibroblasts. Science. 277:831–834. 1997. View Article : Google Scholar : PubMed/NCBI

28 

Herbig U, Wei W, Dutriaux A, Jobling WA and Sedivy JM: Real-time imaging of transcriptional activation in live cells reveals rapid up-regulation of the cyclin-dependent kinase inhibitor gene CDKN1A in replicative cellular senescence. Aging Cell. 2:295–304. 2003. View Article : Google Scholar : PubMed/NCBI

29 

Volonte D, Liu Z, Musille PM, Stoppani E, Wakabayashi N, Di YP, Lisanti MP, Kensler TW and Galbiati F: Inhibition of nuclear factor-erythroid 2-related factor (Nrf2) by caveolin-1 promotes stress-induced premature senescence. Mol Biol Cell. 24:1852–1862. 2013. View Article : Google Scholar : PubMed/NCBI

30 

You A, Nam CW, Wakabayashi N, Yamamoto M, Kensler TW and Kwak MK: Transcription factor Nrf2 maintains the basal expression of Mdm2: an implication of the regulation of p53 signaling by Nrf2. Arch Biochem Biophys. 507:356–364. 2011. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Shin J, Jeon H, Park J and Chang M: Epigallocatechin-3-gallate prevents oxidative stress-induced cellular senescence in human mesenchymal stem cells via Nrf2. Int J Mol Med 38: 1075-1082, 2016.
APA
Shin, J., Jeon, H., Park, J., & Chang, M. (2016). Epigallocatechin-3-gallate prevents oxidative stress-induced cellular senescence in human mesenchymal stem cells via Nrf2. International Journal of Molecular Medicine, 38, 1075-1082. https://doi.org/10.3892/ijmm.2016.2694
MLA
Shin, J., Jeon, H., Park, J., Chang, M."Epigallocatechin-3-gallate prevents oxidative stress-induced cellular senescence in human mesenchymal stem cells via Nrf2". International Journal of Molecular Medicine 38.4 (2016): 1075-1082.
Chicago
Shin, J., Jeon, H., Park, J., Chang, M."Epigallocatechin-3-gallate prevents oxidative stress-induced cellular senescence in human mesenchymal stem cells via Nrf2". International Journal of Molecular Medicine 38, no. 4 (2016): 1075-1082. https://doi.org/10.3892/ijmm.2016.2694
Copy and paste a formatted citation
x
Spandidos Publications style
Shin J, Jeon H, Park J and Chang M: Epigallocatechin-3-gallate prevents oxidative stress-induced cellular senescence in human mesenchymal stem cells via Nrf2. Int J Mol Med 38: 1075-1082, 2016.
APA
Shin, J., Jeon, H., Park, J., & Chang, M. (2016). Epigallocatechin-3-gallate prevents oxidative stress-induced cellular senescence in human mesenchymal stem cells via Nrf2. International Journal of Molecular Medicine, 38, 1075-1082. https://doi.org/10.3892/ijmm.2016.2694
MLA
Shin, J., Jeon, H., Park, J., Chang, M."Epigallocatechin-3-gallate prevents oxidative stress-induced cellular senescence in human mesenchymal stem cells via Nrf2". International Journal of Molecular Medicine 38.4 (2016): 1075-1082.
Chicago
Shin, J., Jeon, H., Park, J., Chang, M."Epigallocatechin-3-gallate prevents oxidative stress-induced cellular senescence in human mesenchymal stem cells via Nrf2". International Journal of Molecular Medicine 38, no. 4 (2016): 1075-1082. https://doi.org/10.3892/ijmm.2016.2694
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