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
February 2013 Volume 5 Issue 2

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
February 2013 Volume 5 Issue 2

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

Anticancer effects of 3,3'-diindolylmethane are associated with G1 arrest and mitochondria-dependent apoptosis in human nasopharyngeal carcinoma cells

  • Authors:
    • Yu Xu
    • Jin Zhang
    • Wendan Shi
    • Yun Liu
  • View Affiliations / Copyright

    Affiliations: Department of Otolaryngology, Renmin Hospital, Wuhan University, Wuhan 430060, Hubei, P.R. China, Department of Gastroenterology, Renmin Hospital, Wuhan University, Wuhan 430060, Hubei, P.R. China
  • Pages: 655-662
    |
    Published online on: December 5, 2012
       https://doi.org/10.3892/ol.2012.1063
  • 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

The antitumor effects of 3,3'-diindolylmethane (DIM) are exhibited in a number of human cancer cells. However, there have been few studies performed concerning the effect of DIM on nasopharyngeal cancer (NPC) cells. In the present study, we examined the in vitro antitumor activity of DIM on the poorly differentiated NPC cell line CNE-2. The potential molecular mechanisms of the activity were also explored. CNE-2 cells were treated with varying concentrations of DIM for different times. Cell proliferation and apoptosis were detected and the molecular mechanisms involved in these effects were characterized. The results demonstrated that DIM at concentrations of 15-100 µM caused dose- and time-dependent inhibition of CNE-2 cell proliferation. Flow cytometry analysis revealed a high sub-G1 cell peak following treatment with DIM, and the rate of apoptosis increased. DIM may elevate the levels of cleaved Bid and Bax and enhance mitochondrial membrane depolarization, allowing the efflux of cytochrome c, Smac and Omi into the cytosol. The levels of caspases-3, -8 and -9 and cleaved poly (ADP-ribose) polymerase (PARP) were upregulated following DIM treatment in a dose‑dependent manner. DIM also inhibits the phosphorylation of IκB-α, and showed dose-dependent inhibition of Bcl-2, XIAP and NF-κB in CNE-2 cells in vitro. These results indicate that DIM inhibits cell proliferation by inducing cell cycle arrest at G0/G1 phase and induces the apoptosis of CNE-2 cells by regulating multiple molecules in a mitochondria-dependent pathway. DIM may be a preventive and therapeutic agent against NPC.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1. 

Cho WC: Nasopharyngeal carcinoma: molecular biomarker discovery and progress. Mol Cancer. 6:12007. View Article : Google Scholar : PubMed/NCBI

2. 

Marks JE, Phillips JL and Menck HR: The National Cancer Data Base report on the relationship of race and national origin to the histology of nasopharyngeal carcinoma. Cancer. 83:582–588. 1998. View Article : Google Scholar : PubMed/NCBI

3. 

Busson P, Keryer C, Ooka T and Corbex M: EBV-associated nasopharyngeal carcinomas: from epidemiology to virus-targeting strategies. Trends Microbiol. 12:356–360. 2004. View Article : Google Scholar : PubMed/NCBI

4. 

Scott EN, Gescher AJ, Steward WP and Brown K: Development of dietary phytochemical chemopreventive agents: biomarkers and choice of dose for early clinical trials. Cancer Prev Res (Phila). 2:525–530. 2009. View Article : Google Scholar : PubMed/NCBI

5. 

Tan AC, Konczak I, Sze DM and Ramzan I: Molecular pathways for cancer chemoprevention by dietary phytochemicals. Nutr Cancer. 63:495–505. 2011. View Article : Google Scholar : PubMed/NCBI

6. 

Sarkar FH, Li Y, Wang Z and Kong D: Cellular signaling perturbation by natural products. Cell Signal. 21:1541–1547. 2009. View Article : Google Scholar : PubMed/NCBI

7. 

Xu Y, Zhang J and Dong WG: Indole-3-carbinol (I3C)-induced apoptosis in nasopharyngeal cancer cells through Fas/FasL and MAPK pathway. Med Oncol. 28:1343–1348. 2011. View Article : Google Scholar : PubMed/NCBI

8. 

Grose KR and Bjeldanes LF: Oligomerization of indole-3-carbinol in aqueous acid. Chem Res Toxicol. 5:188–193. 1992. View Article : Google Scholar : PubMed/NCBI

9. 

Bradlow HL and Zeligs MA: Diindolylmethane (DIM) spontaneously forms from indole-3-carbinol (I3C) during cell culture experiments. In Vivo. 24:387–391. 2010.PubMed/NCBI

10. 

Garikapaty VP, Ashok BT, Tadi K, Mittelman A and Tiwari RK: 3,3′-Diindolylmethane downregulates pro-survival pathway in hormone independent prostate cancer. Biochem Biophys Res Commun. 340:718–725. 2006.

11. 

Nachshon-Kedmi M, Yannai S and Fares FA: Induction of apoptosis in human prostate cancer cell line, PC3, by 3,3′-diindolylmethane through the mitochondrial pathway. Br J Cancer. 91:1358–1363. 2004.

12. 

Rahman KW and Sarkar FH: Inhibition of nuclear translocation of nuclear factor-{kappa}B contributes to 3,3′-diindolylmethane-induced apoptosis in breast cancer cells. Cancer Res. 65:364–371. 2005.

13. 

Hong C, Kim HA, Firestone GL and Bjeldanes LF: 3,3′-Diindolylmethane (DIM) induces a G(1) cell cycle arrest in human breast cancer cells that is accompanied by Sp1-mediated activation of p21 (WAF1/CIP1) expression. Carcinogenesis. 23:1297–1305. 2002.

14. 

Kim EJ, Park SY, Shin HK, Kwon DY, Surh YJ and Park JH: Activation of caspase-8 contributes to 3,3′-Diindolylmethane-induced apoptosis in colon cancer cells. J Nutr. 137:31–36. 2007.

15. 

Weng JR, Bai LY, Chiu CF, Wang YC and Tsai MH: The dietary phytochemical 3,3′-diindolylmethane induces G2/M arrest and apoptosis in oral squamous cell carcinoma by modulating Akt-NF-κB, MAPK, and p53 signaling. Chem Biol Interact. 195:224–230. 2012.

16. 

Adams JM: Ways of dying: multiple pathways to apoptosis. Genes Dev. 17:2481–2495. 2003. View Article : Google Scholar : PubMed/NCBI

17. 

Hengartner MO: The biochemistry of apoptosis. Nature. 407:770–776. 2000. View Article : Google Scholar : PubMed/NCBI

18. 

Tavani A and La Vecchia C: Fruit and vegetable consumption and cancer risk in a Mediterranean population. Am J Clin Nutr. 61(6 Suppl): 1374S–1377S. 1995.PubMed/NCBI

19. 

Wang ZB, Liu YQ and Cui YF: Pathways to caspase activation. Cell Biol Int. 29:489–496. 2005. View Article : Google Scholar : PubMed/NCBI

20. 

Cohen JH, Kristal AR and Stanford JL: Fruit and vegetable intakes and prostate cancer risk. J Natl Cancer Inst. 92:61–68. 2000. View Article : Google Scholar : PubMed/NCBI

21. 

Bradfield CA and Bjeldanes LF: Structure-activity relationships of dietary indoles: a proposed mechanism of action as modifiers of xenobiotic metabolism. J Toxicol Environ Health. 21:311–323. 1987. View Article : Google Scholar : PubMed/NCBI

22. 

Choi HJ, Lim do Y and Park JH: Induction of G1 and G2/M cell cycle arrests by the dietary compound 3,3′-diindolylmethane in HT-29 human colon cancer cells. BMC Gastroenterol. 9:392009.PubMed/NCBI

23. 

Hanahan D and Weinberg RA: Hallmarks of cancer: the next generation. Cell. 144:646–674. 2011. View Article : Google Scholar : PubMed/NCBI

24. 

Thorburn A: Death receptor-induced cell killing. Cell Signal. 16:139–144. 2004. View Article : Google Scholar

25. 

Liu X, Kim CN, Yang J, Jemmerson R and Wang X: Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell. 86:147–157. 1996. View Article : Google Scholar : PubMed/NCBI

26. 

Von Ahsen O, Waterhouse NJ, Kuwana T, Newmeyer DD and Green DR: The ‘harmless’ release of cytochrome c. Cell Death Differ. 7:1192–1199. 2000.

27. 

Zamzami N, Marchetti P, Castedo M, et al: Reduction in mitochondrial potential constitutes an early irreversible step of programmed lymphocyte death in vivo. J Exp Med. 181:1661–1672. 1995. View Article : Google Scholar : PubMed/NCBI

28. 

Chao DT and Korsmeyer SJ: BCL-2 family: regulators of cell death. Annu Rev Immunol. 16:395–419. 1998. View Article : Google Scholar

29. 

Yip KW and Reed JC: Bcl-2 family proteins and cancer. Oncogene. 27:6398–6406. 2008. View Article : Google Scholar : PubMed/NCBI

30. 

Karin M, Cao Y, Greten FR and Li ZW: NF-kappaB in cancer: from innocent bystander to major culprit. Nat Rev Cancer. 2:301–310. 2002. View Article : Google Scholar : PubMed/NCBI

31. 

Wang CY, Mayo MW, Korneluk RG, Goeddel DV and Baldwin AS Jr: NF-κB antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation. Science. 281:1680–1683. 1998.

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Xu Y, Zhang J, Shi W and Liu Y: Anticancer effects of 3,3'-diindolylmethane are associated with G1 arrest and mitochondria-dependent apoptosis in human nasopharyngeal carcinoma cells . Oncol Lett 5: 655-662, 2013.
APA
Xu, Y., Zhang, J., Shi, W., & Liu, Y. (2013). Anticancer effects of 3,3'-diindolylmethane are associated with G1 arrest and mitochondria-dependent apoptosis in human nasopharyngeal carcinoma cells . Oncology Letters, 5, 655-662. https://doi.org/10.3892/ol.2012.1063
MLA
Xu, Y., Zhang, J., Shi, W., Liu, Y."Anticancer effects of 3,3'-diindolylmethane are associated with G1 arrest and mitochondria-dependent apoptosis in human nasopharyngeal carcinoma cells ". Oncology Letters 5.2 (2013): 655-662.
Chicago
Xu, Y., Zhang, J., Shi, W., Liu, Y."Anticancer effects of 3,3'-diindolylmethane are associated with G1 arrest and mitochondria-dependent apoptosis in human nasopharyngeal carcinoma cells ". Oncology Letters 5, no. 2 (2013): 655-662. https://doi.org/10.3892/ol.2012.1063
Copy and paste a formatted citation
x
Spandidos Publications style
Xu Y, Zhang J, Shi W and Liu Y: Anticancer effects of 3,3'-diindolylmethane are associated with G1 arrest and mitochondria-dependent apoptosis in human nasopharyngeal carcinoma cells . Oncol Lett 5: 655-662, 2013.
APA
Xu, Y., Zhang, J., Shi, W., & Liu, Y. (2013). Anticancer effects of 3,3'-diindolylmethane are associated with G1 arrest and mitochondria-dependent apoptosis in human nasopharyngeal carcinoma cells . Oncology Letters, 5, 655-662. https://doi.org/10.3892/ol.2012.1063
MLA
Xu, Y., Zhang, J., Shi, W., Liu, Y."Anticancer effects of 3,3'-diindolylmethane are associated with G1 arrest and mitochondria-dependent apoptosis in human nasopharyngeal carcinoma cells ". Oncology Letters 5.2 (2013): 655-662.
Chicago
Xu, Y., Zhang, J., Shi, W., Liu, Y."Anticancer effects of 3,3'-diindolylmethane are associated with G1 arrest and mitochondria-dependent apoptosis in human nasopharyngeal carcinoma cells ". Oncology Letters 5, no. 2 (2013): 655-662. https://doi.org/10.3892/ol.2012.1063
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