Skip to main content
SpringerLink
Log in

Anti-tumor effect of Cordyceps militaris in HCV-infected human hepatocarcinoma 7.5 cells

  • Microbial Pathogenesis and Host-Microbe Interaction
  • Published:
Journal of Microbiology Aims and scope Submit manuscript

Abstract

Cordyceps extract has been reported to have various pharmacological activities including an anti-cancer effect. We investigated the inhibitory effect of Cordyceps militaris on hepatitis C virus-infected human hepatocarcinoma 7.5 cells (J6/JFH1-huh 7.5 cells). The huh7.5 cells with or without HCV infection were treated with various concentrations of ethanol extract of Cordyceps militaris (CME) for 48 h and the cytotoxicity was measured by CCK-8 assay. Both J6/JFH1-huh7.5 cells and huh7.5 cells were highly susceptible to CME. To examine the molecular mechanisms of the inhibitory effect on huh7.5 cells, the effect of CME on cell apoptosis was measured using flow cytometry and the expressions of p53, Bim, Bax, PARP, (cleaved) caspase-9, and (cleaved) caspase- 3 in huh 7.5 cells were detected by western blot assays. CME significantly increased early apoptosis and up-regulated the expression of Bim, Bax, cleaved PARP, cleaved caspase 9 and cleaved caspase-3. We also found the decrease of HCV Core or NS3 protein by CME in HCV-infected huh 7.5 cells.

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

Similar content being viewed by others

References

  • Adrain C., Slee E.A., Harte M.T., and Martin S.J. 1999. Regulation of apoptotic protease activating factor-1 oligomerization and apoptosis by the wd-40 repeat region. J. Biol. Chem. 274, 20855–20860.

    Article  CAS  PubMed  Google Scholar 

  • Ahn S., Hyeon J., and Park C.K. 2013. Metadherin is a prognostic predictor of hepatocellular carcinoma after curative hepatectomy. Gut Liver 7, 206–212.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Binder M., Kochs G., Bartenschlager R., and Lohmann V. 2007. Hepatitis c virus escape from the interferon regulatory factor 3 pathway by a passive and active evasion strategy. Hepatology 46, 1365–1374.

    Article  CAS  PubMed  Google Scholar 

  • Blight K.J., McKeating J.A., and Rice C.M. 2002. Highly permissive cell lines for subgenomic and genomic hepatitis c virus RNA replication. J. Virol. 76, 13001–13014.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Boulares A.H., Yakovlev A.G., Ivanova V., Stoica B.A., Wang G., Iyer S., and Smulson M. 1999. Role of poly(ADP-ribose) polymerase (PARP) cleavage in apoptosis. Caspase 3-resistant PARP mutant increases rates of apoptosis in transfected cells. J. Biol. Chem. 274, 22932–22940.

    Article  CAS  PubMed  Google Scholar 

  • Cain K., Brown D.G., Langlais C., and Cohen G.M. 1999. Caspase activation involves the formation of the aposome, a large (approximately 700 kDa) caspase-activating complex. J. Biol. Chem. 274, 22686–22692.

    Article  CAS  PubMed  Google Scholar 

  • El-Serag H.B. and Rudolph K.L. 2007. Hepatocellular carcinoma: Epidemiology and molecular carcinogenesis. Gastroenterology 132, 2557–2576.

    Article  CAS  PubMed  Google Scholar 

  • Kim S.P., Nam S.H., and Friedman M. 2013. Hericium erinaceus (Lion’s Mane) mushroom extracts inhibit metastasis of cancer cells to the lung in CT-26 colon cancer-tansplanted mice. J. Agric. Food Chem. 61, 4898–4904.

    Article  CAS  PubMed  Google Scholar 

  • Kim B.S. and Park Y.M. 1993. Prevalence of hepatitis C virus related to liver diseases in Korea. Gastroenterologia Japonica 28 Suppl 5, 17–22.

    Article  PubMed  Google Scholar 

  • Kunjadia P.D., Nagee A., Pandya P.Y., Mukhopadhyaya P.N., Sanghvi G.V., and Dave G.S. 2014. Medicinal and antimicrobial role of the oyster culinary-medicinal mushroom Pleurotus ostreatus (higher Basidiomycetes) cultivated on banana agrowastes in India. Int. J. Med. Mushrooms 16, 227–238.

    Article  PubMed  Google Scholar 

  • Lakin N.D. and Jackson S.P. 1999. Regulation of p53 in response to DNA damage. Oncogene 18, 7644–7655.

    Article  CAS  PubMed  Google Scholar 

  • Lauer G.M. and Walker B.D. 2001. Hepatitis c virus infection. N Eng. J. Med. 345, 41–52.

    Article  CAS  Google Scholar 

  • Lee H.H., Jeong J.W., Lee J.H., Kim G.Y., Cheong J., Jeong Y.K., Yoo Y.H., and Choi Y.H. 2013. Cordycepin increases sensitivity of Hep3B human hepatocellular carcinoma cells to TRAIL-mediated apoptosis by inactivating the JNK signaling pathway. Oncol. Rep. 30, 1257–1264.

    CAS  PubMed  Google Scholar 

  • Lee H., Kim Y.J., Kim H.W., Lee D.H., Sung M.K., and Park T. 2006. Induction of apoptosis by Cordyceps militaris through activation of caspase-3 in leukemia HL-60 cells. Biol. Pharm. Bull. 29, 670–674.

    Article  CAS  PubMed  Google Scholar 

  • Lee H.H., Park H., Sung G.H., Lee K., Lee T., Lee I., Park M.S., Jung Y.W., Shin Y.S., Kang H., et al. 2014. Anti-influenza effect of Cordyceps militaris through immunomodulation in a DBA/2 mouse model. J. Microbiol. 52, 696–701.

    Article  PubMed  Google Scholar 

  • Liang T.J., Rehermann B., Seeff L.B., and Hoofnagle J.H. 2000. Pathogenesis, natural history, treatment, and prevention of hepatitis C. Ann. Intern. Med. 132, 296–305.

    Article  CAS  PubMed  Google Scholar 

  • Ling C.Q., Yue X.Q., and Ling C. 2014. Three advantages of using traditional Chinese medicine to prevent and treat tumor. J. Integr. Med. 12, 331–335.

    Article  PubMed  Google Scholar 

  • Lu H., Li X., Zhang J., Shi H., Zhu X., and He X. 2014. Effects of cordycepin on HepG2 and EA.hy926 cells: Potential antiproliferative, antimetastatic and anti-angiogenic effects on hepatocellular carcinoma. Oncol. Lett. 7, 1556–1562.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Maluccio M. and Covey A. 2012. Recent progress in understanding, diagnosing, and treating hepatocellular carcinoma. CA Cancer J. Clin. 62, 394–399.

    Article  PubMed  Google Scholar 

  • Murphy K.M., Ranganathan V., Farnsworth M.L., Kavallaris M., and Lock R.B. 2000. Bcl-2 inhibits Bax translocation from cytosol to mitochondria during drug-induced apoptosis of human tumor cells. Cell Death Differ. 7, 102–111.

    Article  CAS  PubMed  Google Scholar 

  • Nakabayashi H., Taketa K., Miyano K., Yamane T., and Sato J. 1982. Growth of human hepatoma cells lines with differentiated functions in chemically defined medium. Cancer Res. 42, 3858–3863.

    CAS  PubMed  Google Scholar 

  • Park C., Hong S.H., Lee J.Y., Kim G.Y., Choi B.T., Lee Y.T., Park D.I., Park Y.M., Jeong Y.K., and Choi Y.H. 2005. Growth inhibition of U937 leukemia cells by aqueous extract of Cordyceps militaris through induction of apoptosis. Oncol. Rep. 13, 1211–1216.

    PubMed  Google Scholar 

  • Son M., Lee M., Ryu E., Moon A., Jeong C.S., Jung Y.W., Park G.H., Sung G.H., Cho H., and Kang H. 2015. Genipin as a novel chemical activator of EBV lytic cycle. J. Microbiol. 53, 155–165.

    Article  CAS  PubMed  Google Scholar 

  • Sun Y.S., Lv L.X., Zhao Z., He X., You L., Liu J.K., and Li Y.Q. 2014. Cordycepol C induces caspase-independent apoptosis in human hepatocellular carcinoma HepG2 cells. Biol. Pharm. Bull. 37, 608–617.

    Article  CAS  PubMed  Google Scholar 

  • Tuli H.S., Sharma A.K., Sandhu S.S., and Kashyap D. 2013. Cordycepin: A bioactive metabolite with therapeutic potential. Life Sci. 93, 863–869.

    Article  CAS  PubMed  Google Scholar 

  • Ueda Y., Mori K., Satoh S., Dansako H., Ikeda M., and Kato N. 2014. Anti-HCV activity of the Chinese medicinal fungus Cordyceps militaris. Biochem. Biophys. Res. Commun. 447, 341–345.

    Article  CAS  PubMed  Google Scholar 

  • Wakita T., Pietschmann T., Kato T., Date T., Miyamoto M., Zhao Z., Murthy K., Habermann A., Krausslich H.G., Mizokami M., et al. 2005. Production of infectious hepatitis C virus in tissue culture from a cloned viral genome. Nat. Med. 11, 791–796.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wang B.J., Won S.J., Yu Z.R., and Su C.L. 2005. Free radical scavenging and apoptotic effects of Cordyceps sinensis fractionated by supercritical carbon dioxide. Food Chem. Toxicol. 43, 543–552.

    Article  CAS  PubMed  Google Scholar 

  • Wang H., Zhang J., Sit W.H., Lee C.Y., and Wan J.M. 2014. Cordyceps cicadae induces G2/M cell cycle arrest in MHCC97H human hepatocellular carcinoma cells: A proteomic study. Chin. Med. 9, 15.

    Article  PubMed Central  PubMed  Google Scholar 

  • Wu X. and Deng Y. 2002. Bax and BH3-domain-only proteins in p53-mediated apoptosis. Front. Biosci. 7, d151–156.

    Article  Google Scholar 

  • Yang Y., Hu J., Liu Y., Feng N., Chen H., Tang Q., Ye L., and Zhang J. 2011. Antioxidant and cytotoxic activities of ethanolic extracts and isolated fractions of species of the genus Phellinus Quél. (Aphyllophoromycetideae). Int. J. Med. Mushrooms 13, 145–152.

    Article  PubMed  Google Scholar 

  • Yue K., Ye M., Zhou Z., Sun W., and Lin X. 2013. The genus Cordyceps: A chemical and pharmacological review. J. Pharm. Pharmacol. 65, 474–493.

    Article  CAS  PubMed  Google Scholar 

  • Zhai X.F., Chen Z., Li B., Shen F., Fan J., Zhou W.P., Yang Y.K., Xu J., Qin X., Li L.Q., et al. 2013. Traditional herbal medicine in preventing recurrence after resection of small hepatocellular carcinoma: A multicenter randomized controlled trial. J. Integr. Med. 11, 90–100.

    Article  PubMed  Google Scholar 

  • Zhang W., Li J., Qiu S., Chen J., and Zheng Y. 2008. Effects of the exopolysaccharide fraction (EPSF) from a cultivated Cordyceps sinensis on immunocytes of H22 tumor bearing mice. Fitoterapia 79, 168–173.

    Article  PubMed  Google Scholar 

  • Zhao Y.Y., Shen X., Chao X., Ho C.C., Cheng X.L., Zhang Y., Lin R.C., Du K.J., Luo W.J., Chen J.Y., et al. 2011. Ergosta-4,6, 8(14),22-tetraen-3-one induces G2/M cell cycle arrest and apoptosis in human hepatocellular carcinoma HepG2 cells. Biochim. Biophys. Acta. 1810, 384–390.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. College of Pharmacy, Duksung Women’s University, Seoul, 132-714, Republic of Korea

    Seulki Lee, Hwan Hee Lee, Jisung Kim, Joohee Jung, Aree Moon, Choon-Sik Jeong & Hyosun Cho

  2. Innovative Drug Center, Duksung Women’s University, Seoul, 132-714, Republic of Korea

    Seulki Lee, Hwan Hee Lee, Joohee Jung, Aree Moon, Choon-Sik Jeong & Hyosun Cho

  3. College of Pharmacy, Research Institute of Pharmaceutical Sciences and Institute for Microorganisms, Kyungpook National University, Daegu, 702-701, Republic of Korea

    Hyojeung Kang

Authors
  1. Seulki Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hwan Hee Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jisung Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Joohee Jung
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Aree Moon
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Choon-Sik Jeong
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hyojeung Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hyosun Cho
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Hyojeung Kang or Hyosun Cho.

Additional information

These authors contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lee, S., Lee, H.H., Kim, J. et al. Anti-tumor effect of Cordyceps militaris in HCV-infected human hepatocarcinoma 7.5 cells. J Microbiol. 53, 468–474 (2015). https://doi.org/10.1007/s12275-015-5198-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12275-015-5198-x

Keywords

Search

Navigation