[go: up one dir, main page]
More Web Proxy on the site http://driver.im/ Skip to main content
Springer Nature Link
Log in

Caffeine inhibits hepatitis C virus replication in vitro

  • Original Article
  • Published:
Archives of Virology Aims and scope Submit manuscript

Abstract

Hepatitis C is considered the major cause of cirrhosis and hepatocellular carcinoma. Conventional treatment is not effective against some hepatitis C virus (HCV) genotypes; therefore, new treatments are needed. Coffee and, more recently, caffeine, have been found to have a beneficial effect in several disorders of the liver, including those manifesting abnormal liver biochemistry, cirrhosis and hepatocellular carcinoma. Caffeine acts directly by delaying fibrosis, thereby improving the function of liver cellular pathways and interfering with pathways used by the HCV replication cycle. In the current study, the direct relationship between caffeine and viral replication was evaluated. The Huh-7.5 cell line was used for transient infections with FL-J6/JFH-5′C19Rluc2AUbi and to establish a cell line stably expressing SGR-Feo JFH-1. Caffeine efficiently inhibited HCV replication in a dose-dependent manner at non-cytotoxic concentrations and demonstrated an IC50 value of 0.7263 mM after 48 h of incubation. These data demonstrate that caffeine may be an important new agent for anti-HCV therapies due to its efficient inhibition of HCV replication at non-toxic concentrations.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
£29.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (United Kingdom)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Amako Y, Syed GH, Siddiqui A (2011) Protein kinase D negatively regulates hepatitis C virus secretion through phosphorylation of oxysterol-binding protein and ceramide transfer protein. J Biol Chem 286:11265–11274

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. Beran RK, Sharma R, Corsa AC, Tian Y, Golde J, Lundgaard G, Delaney WEt, Zhong W, Greenstein AE (2012) Cellular growth kinetics distinguish a cyclophilin inhibitor from an HSP90 inhibitor as a selective inhibitor of hepatitis C virus. PLoS ONE 7:e30286

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Cadden IS, Partovi N, Yoshida EM (2007) Review article: possible beneficial effects of coffee on liver disease and function. Aliment Pharmacol Ther 26:1–8

    Article  CAS  PubMed  Google Scholar 

  4. Chevaliez S, Pawlotsky JM (2007) Hepatitis C virus: virology, diagnosis and management of antiviral therapy. World J Gastroenterol 13:2461–2466

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M (1989) Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science 244:359–362

    Article  CAS  PubMed  Google Scholar 

  6. Costentin CE, Roudot-Thoraval F, Zafrani ES, Medkour F, Pawlotsky JM, Mallat A, Hezode C (2011) Association of caffeine intake and histological features of chronic hepatitis C. J Hepatol 54:1123–1129

    Article  CAS  PubMed  Google Scholar 

  7. Ding Q, Bao J, Zhao W, Hu Y, Lu J, Chen X (2014) Natural autophagy regulators in cancer therapy: a review. Phytochem Rev

  8. Dreux M, Gastaminza P, Wieland SF, Chisari FV (2009) The autophagy machinery is required to initiate hepatitis C virus replication. Proc Natl Acad Sci USA 106:14046–14051

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Eom Y, Kim MA, Park SS, Goo MJ, Kwon HJ, Sohn S, Kim W, Yoon GK, Choi KS (2005) Two distinct modes of cell death induced by doxorubicin: apoptosis and cell death through mitotic catastrophe accompanied by senescence-like phenotype. Oncogene 24:4765–4777

    Article  CAS  PubMed  Google Scholar 

  10. Freedman ND, Everhart JE, Lindsay KL, Ghany MG, Curto TM, Shiffman ML, Lee WM, Lok AS, Di Bisceglie AM, Bonkovsky HL, Hoefs JC, Dienstag JL, Morishima C, Abnet CC, Sinha R, Group H-CT (2009) Coffee intake is associated with lower rates of liver disease progression in chronic hepatitis C. Hepatology 50:1360–1369

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Gretton S, Hughes M, Harris M (2010) Hepatitis C virus RNA replication is regulated by Ras-Erk signalling. J Gen Virol 91:671–680

    Article  CAS  PubMed  Google Scholar 

  12. Halfon P, Locarnini S (2011) Hepatitis C virus resistance to protease inhibitors. J Hepatol 55:192–206

    Article  CAS  PubMed  Google Scholar 

  13. Hoofnagle JH (2002) Course and outcome of hepatitis C. Hepatology 36:S21–S29

    Article  PubMed  Google Scholar 

  14. Kang CH, Jayasooriya RG, Dilshara MG, Choi YH, Jeong YK, Kim ND, Kim GY (2012) Caffeine suppresses lipopolysaccharide-stimulated BV2 microglial cells by suppressing Akt-mediated NF-kappaB activation and ERK phosphorylation. Food Chem Toxicol 50:4270–4276

    Article  CAS  PubMed  Google Scholar 

  15. Kang NJ, Lee KW, Kim BH, Bode AM, Lee HJ, Heo YS, Boardman L, Limburg P, Lee HJ, Dong Z (2011) Coffee phenolic phytochemicals suppress colon cancer metastasis by targeting MEK and TOPK. Carcinogenesis 32:921–928

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Kawano Y, Nagata M, Kohno T, Ichimiya A, Iwakiri T, Okumura M, Arimori K (2012) Caffeine increases the antitumor effect of Cisplatin in human hepatocellular carcinoma cells. Biol Pharm Bull 35:400–407

    Article  CAS  PubMed  Google Scholar 

  17. Kieffer TL, Kwong AD, Picchio GR (2010) Viral resistance to specifically targeted antiviral therapies for hepatitis C (STAT-Cs). J Antimicrob Chemother 65:202–212

    Article  CAS  PubMed  Google Scholar 

  18. Kumari SR, Mendonza- Alvarez H, Alvarez-Gonzales R (1998) Functional interactions of p53 with poly(ADP-ribose) polymerase (PARP) during apoptosis following DNA damage: covalent poly(ADP-ribosyl)ation of p5 by exogenous PARP and noncovalent binding of p53 to the Mr 85,000 proteolytic fragment. Cancer Res 58:5075–5078

    CAS  PubMed  Google Scholar 

  19. Lavanchy D (2011) Evolving epidemiology of hepatitis C virus. Clin Microbiol Infect 17:107–115

    Article  CAS  PubMed  Google Scholar 

  20. Lee JC, Chen WC, Wu SF, Tseng CK, Chiou CY, Chang FR, Hsu SH, Wu YC (2011) Anti-hepatitis C virus activity of Acacia confusa extract via suppressing cyclooxygenase-2. Antiviral Res 89:35–42

    Article  CAS  PubMed  Google Scholar 

  21. Lin YT, Wu YH, Tseng CK, Lin CK, Chen WC, Hsu YC, Lee JC (2013) Green tea phenolic epicatechins inhibit hepatitis C virus replication via cycloxygenase-2 and attenuate virus-induced inflammation. PLoS ONE 8:e54466

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Lindenbach BD, Evans MJ, Syder AJ, Wolk B, Tellinghuisen TL, Liu CC, Maruyama T, Hynes RO, Burton DR, McKeating JA, Rice CM (2005) Complete replication of hepatitis C virus in cell culture. Science 309:623–626

    Article  CAS  PubMed  Google Scholar 

  23. Lu PZ, Lai CY, Chan WH (2008) Caffeine induces cell death via activation of apoptotic signal and inactivation of survival signal in human osteoblasts. Int J Mol Sci 9:698–718

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Modi AA, Feld JJ, Park Y, Kleiner DE, Everhart JE, Liang TJ, Hoofnagle JH (2010) Increased caffeine consumption is associated with reduced hepatic fibrosis. Hepatology 51:201–209

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Mohl BP, Tedbury PR, Griffin S, Harris M (2012) Hepatitis C virus-induced autophagy is independent of the unfolded protein response. J Virol 86:10724–10732

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Nakagawa S, Umehara T, Matsuda C, Kuge S, Sudoh M, Kohara M (2007) Hsp90 inhibitors suppress HCV replication in replicon cells and humanized liver mice. Biochem Biophys Res Commun 353:882–888

    Article  CAS  PubMed  Google Scholar 

  27. Okamoto T, Nishimura Y, Ichimura T, Suzuki K, Miyamura T, Suzuki T, Moriishi K, Matsuura Y (2006) Hepatitis C virus RNA replication is regulated by FKBP8 and Hsp90. EMBO J 25:5015–5025

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Okano J, Nagahara T, Matsumoto K, Murawaki Y (2008) Caffeine inhibits the proliferation of liver cancer cells and activates the MEK/ERK/EGFR signalling pathway. Basic Clin Pharmacol Toxicol 102:543–551

    Article  CAS  PubMed  Google Scholar 

  29. Pawlotsky JM (2012) New antiviral agents for hepatitis C. F1000 Biol Rep 4:5

    Article  PubMed Central  PubMed  Google Scholar 

  30. Ruhl CE, Everhart JE (2005) Coffee and caffeine consumption reduce the risk of elevated serum alanine aminotransferase activity in the United States. Gastroenterology 128:24–32

    Article  CAS  PubMed  Google Scholar 

  31. Sinha RA, Farah BL, Singh BK, Siddique MM, Li Y, Wu Y, Ilkayeva OR, Gooding J, Ching J, Zhou J, Martinez L, Xie S, Bay BH, Summers SA, Newgard CB, Yen PM (2014) Caffeine stimulates hepatic lipid metabolism by the autophagy-lysosomal pathway in mice. Hepatology 59:1366–1380

    Article  CAS  PubMed  Google Scholar 

  32. Tao Z, Jones E, Goodisman J, Souid AK (2008) Quantitative measure of cytotoxicity of anticancer drugs and other agents. Anal Biochem 381:43–52

    Article  CAS  PubMed  Google Scholar 

  33. Tscherne DM, Jones CT, Evans MJ, Lindenbach BD, McKeating JA, Rice CM (2006) Time- and temperature-dependent activation of hepatitis C virus for low-pH-triggered entry. J Virol 80:1734–1741

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Van den Hoff MJ, Moorman AF, Lamers WH (1992) Electroporation in ‘intracellular’ buffer increases cell survival. Nucleic Acids Res 20:2902

    Article  PubMed Central  PubMed  Google Scholar 

  35. Vermehren J, Sarrazin C (2012) The role of resistance in HCV treatment. Best Pract Res Clin Gastroenterol 26:487–503

    Article  CAS  PubMed  Google Scholar 

  36. Wyles DL, Kaihara KA, Korba BE, Schooley RT, Beadle JR, Hostetler KY (2009) The octadecyloxyethyl ester of (S)-9-[3-hydroxy-2-(phosphonomethoxy) propyl]adenine is a potent and selective inhibitor of hepatitis C virus replication in genotype 1A, 1B, and 2A replicons. Antimicrob Agents Chemother 53:2660–2662

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Yi Z, Pan T, Wu X, Song W, Wang S, Xu Y, Rice CM, Macdonald MR, Yuan Z (2011) Hepatitis C virus co-opts Ras-GTPase-activating protein-binding protein 1 for its genome replication. J Virol 85:6996–7004

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Zeitlin R, Patel S, Burgess S, Arendash GW, Echeverria V (2011) Caffeine induces beneficial changes in PKA signaling and JNK and ERK activities in the striatum and cortex of Alzheimer’s transgenic mice. Brain Res 1417:127–136

    Article  CAS  PubMed  Google Scholar 

  39. Zhong J, Gastaminza P, Cheng G, Kapadia S, Kato T, Burton DR, Wieland SF, Uprichard SL, Wakita T, Chisari FV (2005) Robust hepatitis C virus infection in vitro. Proc Natl Acad Sci USA 102:9294–9299

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

The authors are grateful to Professor Mark Harris (University of Leeds, UK) for providing the polyclonal anti-NS5A antibody, and to CAPES (Coordination for the Improvement of Higher Education Personnel) and FAPESP (grant 2012/19074-1 São Paulo Research Foundation) for financial support. The authors would also like to thank all members of the Laboratory of Genomics Studies (IBILCE-UNESP, BR) for their helpful suggestions and discussions.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Biology, Institute of Bioscience, Language and Literature and Exact Science, São Paulo State University, IBILCE, UNESP, Rua Cristóvão Colombo 2265, São José do Rio Preto, SP, 15054-000, Brazil

    Mariana N. Batista, Bruno M. Carneiro, Ana Cláudia S. Braga & Paula Rahal

Authors
  1. Mariana N. Batista
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bruno M. Carneiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ana Cláudia S. Braga
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Paula Rahal
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Paula Rahal.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 1244 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Batista, M.N., Carneiro, B.M., Braga, A.C.S. et al. Caffeine inhibits hepatitis C virus replication in vitro . Arch Virol 160, 399–407 (2015). https://doi.org/10.1007/s00705-014-2302-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00705-014-2302-1

Keywords

Search

Navigation