Skip to main content
SpringerLink
Log in

Cytotoxic Effect of Fusarium Equiseti Fungus Metabolites Against N-Nitrosodiethylamine- and CCL4-Induced Hepatocarcinogenesis in Rats

  • Published:
Pharmaceutical Chemistry Journal Aims and scope

Fusarium equiseti, an endophytic fungus isolated from the marine alga Padina pavonica, displayed in vitro potent cytotoxicity and selectivity against liver cancer (HEP-G2) cells. This endophyte was therefore submitted to large-scale liquid fermentation to isolate 11 bioactive constituents. The cytotoxic effect of the extract against in vivo hepatocellular carcinoma (HCC) was evaluated in rats with HCC induced by single intraperitoneal injection of N-nitrosodiethylamine (NDEA) followed by subcutaneous injections of CCl4. After the injection of carcinogen, the fungal extract was orally administered in 25, 50 and 100 mg/kg doses once a day for 10 weeks. The high levels of liver injury and liver cancer markers after NDEA administration were significantly decreased by this treatment with the total fungal metabolites. Histological observations of the liver tissues of rats treated with NDEA and fungal extract co-administered at 100 mg/kg are correlated with the biochemical observations. These findings confirm that F. equiseti total metabolites could restore the activity of hepatic marker enzymes of NDEA-induced hepatocarcinogenesis in rats.

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.

Similar content being viewed by others

References

  1. F. X. Bosch, J. Ribes, R. Cleries, et al., Clin. Liver Dis., 9(2), 191 – 211 (2005).

    Article  PubMed  Google Scholar 

  2. V. Sivaramakrishnan, P. M. Shilpa, V. P. Kumar, et al., Chem. Biol. Interact., 171(1), 79 – 88 (2008).

    Article  PubMed  CAS  Google Scholar 

  3. J. G. Macia-Vicente, H. B. Jansson, S. K. Abdullah, et al., FEMS Microbiol. Ecol., 64(1), 90–105 (2008).

    Article  PubMed  CAS  Google Scholar 

  4. X. Weiping, C. J. Mirocha, and Y. Wen., J. Nat. Prod., 54(4), 1165 – 1167 (1991).

    Article  Google Scholar 

  5. D. Dréau, M. Foster, M. Hogg, et al., Anticancer Drugs, 18(8), 897 – 904 (2007).

    PubMed  Google Scholar 

  6. G. G. Kuiper, B. Carlsson, K. Grandien, et al., Endocrinology, 138(3), 863 – 870 (1997).

    Article  PubMed  CAS  Google Scholar 

  7. U. W. Hawas, R. Al-Farawati, L. T. Abou El-Kassem, et al., Mar. Drugs, 14(10), E190 (2016).

    Article  PubMed  CAS  Google Scholar 

  8. S. Sundaresan and P. Subramanian, Pol. J. Pharmacol., 55(1), 37 – 42 (2003).

    PubMed  CAS  Google Scholar 

  9. G. Ramakrishnan, H. B. Raghavendran, R. Vinodhkumar, et al., Chem. Biol. Interact., 161(2), 104 – 114 (2006).

    Article  PubMed  CAS  Google Scholar 

  10. S. Reitman and S. A. Frankel, Am. J. Clin. Pathol., 28, 56 – 63 (1957).

    Article  PubMed  CAS  Google Scholar 

  11. E. J. King and A. R. Armstrong, Can. Med. Assoc. J., 311, 152–156 (1934).

    Google Scholar 

  12. W. G. Dangerfield and R. Finlayson, J. Clin. Pathol., 6(3), 173 – 177 (1953).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. S. Sell and F. F. Beckar, Natl. Cancer Inst., 60(1), 19 – 26 (1978).

    Article  CAS  Google Scholar 

  14. G. M. Macnab, J. M. Urbanowicz, and M. C. Kew, Brit. J. Cancer, 38(1), 51–54 (1978).

    Article  PubMed  CAS  Google Scholar 

  15. R. B. Drury and E. A. Wallington, Carleton’s Histology Technique, 5th edn., Oxford University Press, Oxford (1980).

    Google Scholar 

  16. N. M. M. U. Khan and M. S. Hossain, J. Pharmacogn. Phytochem., 4(2), 5 – 7 (2015).

    Google Scholar 

  17. S. Kiyoto, Y. Kawai, T. Kawakita, et al., J. Antibiot., 39(6), 762 – 772 (1968).

    Article  Google Scholar 

  18. R. A. Cacho, Y. H. Chooi, H. Zhou, et al., ACS. Chem. Biol., 8(10), 2322 – 2330 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. F. Caesar, K. K. Jansson, and E. E. Mutschler, Pharm. Acta. Helv., 44(11), 676 – 690 (1969).

    PubMed  CAS  Google Scholar 

  20. H. Shigemori, M. Tenma, K. Shimazaki, et al., J. Nat. Prod., 61(5), 696–698 (1998).

    Article  PubMed  CAS  Google Scholar 

  21. C. J. Barrow and H. H. Sun, J. Nat. Prod., 57(4), 471–476 (1994).

    Article  PubMed  CAS  Google Scholar 

  22. W. Rungprom, E. R. O. Siwu, L. K. Lambert, et al., Tetrahedron, 64(4), 3147 – 3152 (2008).

    Article  CAS  Google Scholar 

  23. F. Valeriote, C. K. Grieshaber, J. Media, et al., J. Exp. Therap. Oncol., 2(4), 228 – 236 (2002).

    Article  CAS  Google Scholar 

  24. L. Verna, J. Whysner, and G. M. Williams, Pharmacol. Ther., 71(1 – 2), 57 – 81 (1996).

    Article  PubMed  CAS  Google Scholar 

  25. G. M. Rao, C. V. Rao, P. Pushpangadan, et al., J. Ethnopharmacol., 103(3), 484 – 490 (2006).

    Article  PubMed  CAS  Google Scholar 

  26. C. R. Wolf, W. G. Harrelson, W. M. Nastainczyk, et al., Mol. Pharmacol., 18(3), 553 – 558 (1980).

    PubMed  CAS  Google Scholar 

  27. M. Maeda, S. Tozuka, M. Kanayama, et al., Dig. Dis. Sci., 33(12), 1629 – 1631(1988).

    Article  PubMed  CAS  Google Scholar 

  28. M. Munekata and G. Tamura, Agric. Biol. Chem., 45(11), 2613 – 2618 (1981).

    CAS  Google Scholar 

  29. R. Zhu, R. Zheng, Y. Deng, et al., Phytomedicine, 21(3), 372 – 378 (2014).

    Article  PubMed  CAS  Google Scholar 

  30. Q. P. Wu, Y. Z. Xie, Z. Deng, et al., PLoS One, 7(8), e44579 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Prof. Fred Valeriote, Henry Ford Cancer Health System, Detroit, Michigan, USA, for the tests with cell lines. This work was supported by a Basic and Applied Research Grant from the Egyptian Science and Technological Development Fund (STDF, Grant No. 990).

Author information

Authors and Affiliations

  1. Marine Chemistry Department, Faculty of Marine Sciences, King Abdulaziz University, Jeddah, 21589, Kingdom of Saudi Arabia

    Usama W. Hawas

  2. Phytochemistry and Plant Systematic Department, National Research Centre, Cairo, Dokki, 12311, Egypt

    Usama W. Hawas

  3. Pathology Department, National Research Centre, Cairo, Dokki, 12311, Egypt

    Abdel Razik H. Farrag

  4. Chemistry of Natural and Microbial Products Department, National Research Centre, Cairo, Dokki, 12311, Egypt

    Eman F. Ahmed

  5. Pharmacognosy Department, National Research Centre, Cairo, Dokki, 12311, Egypt

    Lamia T. Abou El-Kassem

Authors
  1. Usama W. Hawas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Abdel Razik H. Farrag
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eman F. Ahmed
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lamia T. Abou El-Kassem
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Usama W. Hawas.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hawas, U.W., Farrag, A.R.H., Ahmed, E.F. et al. Cytotoxic Effect of Fusarium Equiseti Fungus Metabolites Against N-Nitrosodiethylamine- and CCL4-Induced Hepatocarcinogenesis in Rats. Pharm Chem J 52, 326–333 (2018). https://doi.org/10.1007/s11094-018-1816-3

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11094-018-1816-3

Keywords

Search

Navigation