Skip to main content
SpringerLink
Log in

Ellagic Acid Normalizes Mitochondrial Outer Membrane Permeabilization and Attenuates Inflammation-Mediated Cell Proliferation in Experimental Liver Cancer

  • Published:
Applied Biochemistry and Biotechnology Aims and scope Submit manuscript

Abstract

Despite great advances in our understanding of the molecular causes of liver cancer, significant gaps still remain in our knowledge of the disease pathogenesis and development of effective strategies for early diagnosis and treatment. The present study was conducted to evaluate the chemopreventive activity of ellagic acid (EA) against experimental liver cancer in rats. This is the first report that implies a possible role of EA in controlling liver cancer through activation of mitochondrial outer membrane permeability via activating proteins such as Bax, bcl-2, cyt-C, and caspase-9, which play important roles in apoptosis. Downregulation of NF-κB, cyclin D1, cyclin E1, matrix metalloproteinases (MMP)-2, MMP-9, and proliferating cell nuclear antigen (PCNA) were noted in EA-treated experimental rats and controlled inflammation mediated liver cancer when compared to the diethylnitrosamine (DEN)-induced group. Transmission electron microscopy (TEM) analysis of the livers of experimental rats demonstrated that EA treatment renovated its internal architecture. Overall, these results demonstrate the value of molecular approaches in identifying the potential role of EA as an effective chemopreventive agent.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Zhao, J. L., Zhao, J., & Jiao, H. J. (2013). Applied Biochemistry and Biotechnology, 172, 784–791.

    Article  Google Scholar 

  2. Khan, M. S., Halagowder, D., & Niranjali, S. D. (2011). Food and Chemical Toxicology, 49, 173–178.

    Article  CAS  Google Scholar 

  3. Ford, N. A., Lashinger, L. M., Allott, E. H., & Hursting, S. D. (2013). Frontiers Oncology, 3, 209.

    Article  Google Scholar 

  4. Jakszyn, P. G., Allen, N. E., Barroso, L. L., et al. (2012). Cancer Epidemiology Biomarkers, 21, 547–551.

    Article  CAS  Google Scholar 

  5. Mittal, G., Brar, A. P., & Soni, G. (2006). Pharmacological Reports, 58, 413–419.

    CAS  Google Scholar 

  6. Mittal, G., Brar, A. P., & Soni, G. (2006). Pharmacological Reports, 58, 413–419.

    CAS  Google Scholar 

  7. Sivaramakrishnan, V., & Devaraj, S. N. (2009). Chemico-Biological Interactions, 180, 353–359.

    Article  CAS  Google Scholar 

  8. Al-Kaseem, M., Al-Assaf, Z., & Karabet, F. (2013). Pharmacology and Pharmacy, 4, 611–618.

    Article  CAS  Google Scholar 

  9. Lee, L., Wang, K., Li, G., Xie, Z., Wang, Y., Xu, J., et al. (2011). BMC Genomics, 12(S3), 1–13.

    CAS  Google Scholar 

  10. Kim, J. Y., Ok, E., Kim, Y. J., Choi, K. S., & Kwon, O. (2013). Nutrition Research and Practice, 7(3), 153–159.

    Article  CAS  Google Scholar 

  11. Umesalma, S., & Sudhandiran, G. (2010). Basic and Clinical Pharmacology and Toxicology, 107, 650–655.

    Article  CAS  Google Scholar 

  12. Jiang, W., Zhu, Z., McGinley, J. N., Bayoumy, K. E., Manni, A., & Thompson, H. J. (2013). Cancer Research, 72(15), 3795–806.

    Article  Google Scholar 

  13. Vanella, L., Giacomo, C. D., Acquaviva, R., Barbagallo, I., Volti, G. L., Cardile, V., et al. (2013). Cancers, 5, 726–738.

    Article  CAS  Google Scholar 

  14. Pittoni, P., & Colombo, M. P. (2012). Cancer Research, 72, 831–835.

    Article  CAS  Google Scholar 

  15. Choi, Y. J., Li, X., Hydbring, P., Sanda, T., Stefano, J., Christie, A. L., et al. (2012). Cancer Cell, 22(4), 438–451.

    Article  CAS  Google Scholar 

  16. Herszényi, L., Hritz, I., Lakatos, G., Varga, M. Z., & Tulassay, Z. (2012). International Journal of Molecular Sciences, 13, 13240–13263.

    Article  Google Scholar 

  17. Srigopalram, S., Ilavenil, S., & Indira, A. J. (2012). Biomedicine and Preventive Nutrition, 2, 1–8.

    Article  Google Scholar 

  18. Nelson, L. J., Treskes, P., Howie, A. F., Walker, S. W., Hayes, P. C., & Plevris, J. N. (2013). Scientific Reports, 3, 2735.

    Article  Google Scholar 

  19. Ranieri, G., Labriola, A., Achille, G., Florio, G., Zito, A. F., & Grammatica, L. (2002). International Journal of Oncology, 21(6), 1317–1323.

    CAS  Google Scholar 

  20. Ramakrishnan, G., Elinos-Baaez, C. M., Jagan, S., Augustine, T. A., Kamaraj, S., Anandakumar, P., et al. (2008). Molecular and Cellular Biochemistry, 313(1–2), 53–61.

    Article  CAS  Google Scholar 

  21. Ramakrishnan, G., Jagan, S., Kamaraj, S., Anandakumar, P., & Devaki, T. (2009). Investigational New Drugs, 27, 233–240.

    Article  CAS  Google Scholar 

  22. Hassoun, E. A., & Cearfoss, J. (2011). Toxicological and Environmental Chemistry, 93(2), 332–344.

    Article  CAS  Google Scholar 

  23. Gounaris, E., Erdman, S. E., Restaino, C., Gurish, M. F., Friend, D. S., & Gounari, F. (2007). Proceedings of the National Academy of Sciences of the United States of America, 104(50), 19977–19982.

    CAS  Google Scholar 

  24. Grizzi, F., Di Caro, G., Laghi, L., Hermonat, P., Mazzola, P., Nquyen, D. D., et al. (2013). Immunity & Ageing, 10(1), 1–10.

    Article  Google Scholar 

  25. Hodges, K., Kennedy, L., Meng, F., Alpini, G., & Francis, H. (2012). Translation of Gastrointestinal Cancer, 1(2), 138–150.

    Google Scholar 

  26. Kang, J. S., Kang, H. G., Park, Y. I., Lee, H., Park, K., Lee, Y. S., et al. (2013). Experimental and Therapeutic Medicine, 5, 138–142.

    CAS  Google Scholar 

  27. Sun, H., Yu, L., Wei, H., & Liu, G. (2012). Journal of Biomedicine & Biotechnology, 2012(584728), 1–9.

    Google Scholar 

  28. Qasim, B. J., Ali, H. H., & Hussein, A. G. (2012). Saudi Journal of Gastroenterology, 18, 268–76.

    Article  Google Scholar 

  29. Zhao, H., Ho, P. C., Lo, Y. H., Espejo, A., Bedford, M. T., Hung, M. C., et al. (2012). PloS One, 7(e29416), 1–7.

    Google Scholar 

  30. Muriel, P. (2009). NF-kB in liver diseases: a target for drug therapy. Journal of Applied Toxicology, 29, 91–100.

    Article  CAS  Google Scholar 

  31. Holdenrieder, S., & Stieber, P. (2004). Clinical Biochemistry, 37, 605–617.

    Article  CAS  Google Scholar 

  32. Rusca, N., Dehò, L., Montagner, S., Zielinski, C. E., Sica, A., Sallusto, F., et al. (2012). Molecular and Cellular Biology, 32, 4432–4444.

    Article  CAS  Google Scholar 

  33. Boström, P., Söderström, M., Palokangas, T., Vahlberg, T., Collan, Y., Carpen, O., et al. (2009). BMC Research Notes, 2(140), 1–8.

    Google Scholar 

  34. Thieringer, F. R., Maass, T., Anthon, B., Meyer, E., Schirmacher, P., Longerich, T., et al. (2012). Molecular Carcinogenesis, 51, 439–448.

    Article  CAS  Google Scholar 

  35. Chantrian, C. F., Henriet, P., Jodele, S., Emonard, H., Feron, O., & Courtoy, P. J. (2006). European Journal of Cancer, 42(3), 310–318.

    Article  Google Scholar 

  36. Huang, X. H., Chen, J. S., Wang, Q., Chen, X. L., Wen, L., Chen, L. Z., et al. (2011). The Journal of Pathology, 225(3), 463–472.

    Article  CAS  Google Scholar 

  37. Partyka, R., Gonciarz, M., Jałowiecki, P., Kokocińska, D., & Byrczek, T. (2012). Medical Science Monitor, 18(4), 130–134.

    Article  Google Scholar 

  38. Lo, S. J., Fan, L. C., Tsai, Y. F., Lin, K. Y., Huang, H. L., Wang, T. H., et al. (2013). Hepatology, 57(5), 1893–1905.

    Article  CAS  Google Scholar 

  39. Yu, J. Q., Bao, W., & Lei, J. C. (2013). Phytotherapy Research, 27, 251–257.

    Article  CAS  Google Scholar 

  40. Zhang, C. Z., Pan, Y., Cao, Y., Lai, P. B. S., Liu, L., Chen, G. G., & Yun (2012). Journal of PLoS ONE, 7(6), e39870, 1–10.

  41. Mahdavi, M., Davoodi, J., Zali, M. R., & Foroumadi, A. (2011). Biomedicine & Pharmacotherapy, 65, 175–182.

    Article  CAS  Google Scholar 

  42. Wang, N., Feng, Y., Zhu, M., Tsang, C. M., Man, K., Tong, Y., et al. (2010). Berberine Induces Autophagic Cell Death and Mitochondrial Apoptosis in Liver Cancer Cells: The Cellular Mechanism. Journal of Cellular Biochemistry, 111, 1426–1436.

    Article  CAS  Google Scholar 

  43. Kang, J. H., Zhang, W. Q., Song, W., Shen, D. Y., Li, S. S., Tian, L., et al. (2012). Applied Biochemistry and Biotechnology, 166(4), 942–51.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This research was supported by Golden Seed Project (Center for Horticultural Seed Development, No. 213003-04-1-CG100), Ministry of Agriculture, Food and Rural Affairs (MAFRA), Ministry of Oceans and Fisheries (MOF), Rural Development Administration (RDA), and Korea Forest Service (KFS).

Conflict of Interest

The authors confirm that there is no conflict of interest associated with this work.

Author information

Authors and Affiliations

  1. Department of Horticulture, Sunchon National University, 255 Jungang-ro, Suncheon, Jeonnam, 540-950, South Korea

    S. Srigopalram, M. Ranjithkumar, T. Senthil Kumar, J. I. Park & I. S. Nou

  2. Department of Biochemistry, Kongunadu Arts and Science College (Autonomous), Coimbatore, Tamil Nadu, India

    I. A. Jayraaj

  3. Department of Zoology & Biotechnology, A.V.V.M. Sri Pushpam College (Autonomous), Thanjavur, Tamil Nadu, India

    B. Kaleeswaran

  4. Department of Biochemistry, PRIST University, Thanjavur, Tamil Nadu, India

    K. Balamurugan

Authors
  1. S. Srigopalram
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. I. A. Jayraaj
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B. Kaleeswaran
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. K. Balamurugan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Ranjithkumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. T. Senthil Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J. I. Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. I. S. Nou
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to I. S. Nou.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Srigopalram, S., Jayraaj, I.A., Kaleeswaran, B. et al. Ellagic Acid Normalizes Mitochondrial Outer Membrane Permeabilization and Attenuates Inflammation-Mediated Cell Proliferation in Experimental Liver Cancer. Appl Biochem Biotechnol 173, 2254–2266 (2014). https://doi.org/10.1007/s12010-014-1031-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12010-014-1031-y

Keywords

Search

Navigation