Skip to main content

Advertisement

SpringerLink
Log in

Pseudomonas aeruginosa: Mannose Sensitive Hemagglutinin Inhibits the Growth of Human Hepatocarcinoma Cells via Mannose-Mediated Apoptosis

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

A vaccine derived from the outer membrane proteins of the Gram-negative bacterium Pseudomonas aeruginosa has been shown to have immune modulatory properties. An inactivated mutant strain of P. aeruginosa with mannose sensitive hemagglutinin fimbria (PA-MSHA) has been used for adjuvant therapy for malignant cancer. In this study, the growth of human hepatocellular carcinoma Hep G2 and BEL-7402 cells is inhibited by PA-MSHA, but not by mannose-cleaved PA-MSHA. PA-MSHA-treated cells arrested in the S phase of the cell cycle and underwent apoptosis. We hypothesize that apoptosis induced by treatment of Hep G2 and BEL-7402 cells with PA-MSHA is mediated by the mannose residues of PA-MSHA and is propagated through the extrinsic apoptosis pathway directly through caspase-8. These data provide mechanistic details for the potential application of PA-MSHA-based treatment of hepatocellular carcinoma.

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. Porwoll JM, Gebel HM, Rodey GE, Markham RB. In vitro response of human T cells to Pseudomonas aeruginosa. Infect Immun. 1983;40:670–674.

    PubMed  CAS  Google Scholar 

  2. Lee N, Ahn B, Jung SB, Kim YG, Kim H, Park WJ. Conformation-dependent antibody response to Pseudomonas aeruginosa outer membrane proteins induced by immunization in humans. FEMS Immunol Med Microbiol. 2000;27:79–85. doi:10.1111/j.1574-695X.2000.tb01415.x.

    Article  PubMed  CAS  Google Scholar 

  3. Mu XY. Success in establishing the MSHA-positive Pseudomonas aeruginosa fimbrial strain. Wei Sheng Wu Xue Bao. 1986;26:176–179.

    PubMed  CAS  Google Scholar 

  4. Jia L, Wang C, Kong H, et al. Effect of PA-MSHA vaccine on plasma phospholipids metabolic profiling and the ratio of Th2/Th1 cells within immune organ of mouse IgA nephropathy. J Pharm Biomed Anal. 2007;43:646–654. doi:10.1016/j.jpba.2006.07.040.

    Article  PubMed  CAS  Google Scholar 

  5. Li Z, Hao D, Zhang H, et al. A clinical study on PA-MSHA vaccine used for adjuvant therapy of lymphoma and lung cancer. Hua Xi Yi Ke Da Xue Xue Bao. 2000;31:334–337.

    PubMed  CAS  Google Scholar 

  6. Lau WY, Lai EC, Leung TW, Yu SC. Adjuvant intra-arterial iodine-131-labeled lipiodol for resectable hepatocellular carcinoma: a prospective randomized trial-update on 5-year and 10-year survival. Ann Surg. 2008;247:43–48.

    Article  PubMed  Google Scholar 

  7. Tan A, Yeh SH, Liu CJ, Cheung C, Chen PJ. Viral hepatocarcinogenesis: from infection to cancer. Liver Int. 2008;28:175–188.

    Article  PubMed  CAS  Google Scholar 

  8. Nayak NC. Hepatocellular carcinoma—a model of human cancer: clinico-pathological features, etiology and pathogenesis. Indian J Pathol Microbiol. 2003;46:1–16.

    PubMed  CAS  Google Scholar 

  9. McKillop IH, Schrum LW. Alcohol and liver cancer. Alcohol. 2005;35:195–203. doi:10.1016/j.alcohol.2005.04.004.

    Article  PubMed  CAS  Google Scholar 

  10. Bruix J, Hessheimer AJ, Forner A, Boix L, Vilana R, Llovet JM. New aspects of diagnosis and therapy of hepatocellular carcinoma. Oncogene. 2006;25:3848–3856. doi:10.1038/sj.onc.1209548.

    Article  PubMed  CAS  Google Scholar 

  11. Roessler S, Budhu A, Wang XW. Future of molecular profiling of human hepatocellular carcinoma. Future Oncol. 2007;3:429–439. doi:10.2217/14796694.3.4.429.

    Article  PubMed  CAS  Google Scholar 

  12. Sell S. Cellular origin of hepatocellular carcinomas. Semin Cell Dev Biol. 2002;13:419–424. doi:10.1016/S1084952102001295.

    Article  PubMed  Google Scholar 

  13. Schulte-Hermann R, Bursch W, Löw-Baselli A, Wagner A, Grasl-Kraupp B. Apoptosis in the liver and its role in hepatocarcinogenesis. Cell Biol Toxicol. 1997;13:339–348. doi:10.1023/A:1007495626864.

    Article  PubMed  CAS  Google Scholar 

  14. Park YN, Chae KJ, Kim YB, Park C, Theise N. Apoptosis and proliferation in hepatocarcinogenesis related to cirrhosis. Cancer. 2001;92:2733–2738. doi:10.1002/1097-0142(20011201)92:11<2733::AID-CNCR10126>3.0.CO;2-5.

    Article  PubMed  CAS  Google Scholar 

  15. Snaith SM, Levvy GA. Purification and properties of alpha-d-mannosidase from jack-bean meal. Biochem J. 1968;110:663–670.

    PubMed  CAS  Google Scholar 

  16. Nahmias Y, Casali M, Barbe L, Berthiaume F, Yarmush ML. Liver endothelial cells promote LDL-R expression and the uptake of HCV-like particles in primary rat and human hepatocytes. Hepatology. 2006;43:257–265. doi:10.1002/hep.21016.

    Article  PubMed  CAS  Google Scholar 

  17. Zhang J, Yu J, Gu J, et al. A novel protein-DNA interaction involved with the CpG dinucleotide at −30 upstream is linked to the DNA methylation mediated transcription silencing of the MAGE-A1 gene. Cell Res. 2004;14:283–294. doi:10.1038/sj.cr.7290229.

    Article  PubMed  CAS  Google Scholar 

  18. Wang J, Zhen L, Klug MG, Wood D, Wu X, Mizrahi J. Involvement of caspase 3- and 8-like proteases in ceramide-induced apoptosis of cardiomyocytes. J Card Fail. 2000;6:243–249. doi:10.1054/jcaf.2000.9502.

    Article  PubMed  CAS  Google Scholar 

  19. Liedtke C, Groger N, Manns MP, Trautwein C. The human caspase-8 promoter sustains basal activity through SP1 and ETS-like transcription factors and can be up-regulated by a p53-dependent mechanism. J Biol Chem. 2003;278:27593–27604. doi:10.1074/jbc.M304077200.

    Article  PubMed  CAS  Google Scholar 

  20. Chalfant CE, Rathman K, Pinkerman RL, et al. De novo ceramide regulates the alternative splicing of caspase 9 and Bcl-x in A549 lung adenocarcinoma cells. Dependence on protein phosphatase-1. J Biol Chem. 2002;277:12587–12595. doi:10.1074/jbc.M112010200.

    Article  PubMed  CAS  Google Scholar 

  21. Caputo R, Tuccillo C, Manzo BA, et al. Helicobacter pylori VacA toxin up-regulates vascular endothelial growth factor expression in MKN 28 gastric cells through an epidermal growth factor receptor-, cyclooxygenase-2-dependent mechanism. Clin Cancer Res. 2003;9:2015–2021.

    PubMed  CAS  Google Scholar 

  22. Philchenkov AA. Caspases as regulators of apoptosis and other cell functions. Biochemistry (Mosc). 2003;68:365–376. doi:10.1023/A:1023635510363.

    Article  CAS  Google Scholar 

  23. Guicciardi ME, Gores GJ. Apoptosis: a mechanism of acute and chronic liver injury. Gut. 2005;54:1024–1033. doi:10.1136/gut.2004.053850.

    Article  PubMed  CAS  Google Scholar 

  24. Mathiasen IS, Jäättelä M. Triggering caspase-independent cell death to combat cancer. Trends Mol Med. 2002;8:212–220. doi:10.1016/S1471-4914(02)02328-6.

    Article  PubMed  CAS  Google Scholar 

  25. Hegardt C, Andersson G, Oredsson SM. Different roles of spermine in glucocorticoid and Fas-induced apoptosis. Exp Cell Res. 2001;266:333–341. doi:10.1006/excr.2001.5230.

    Article  PubMed  CAS  Google Scholar 

  26. Tretiakova I, Blaesius D, Maxia L, et al. Myrtucommulone from Myrtus communis induces apoptosis in cancer cells via the mitochondrial pathway involving caspase-9. Apoptosis. 2008;13:119–131. doi:10.1007/s10495-007-0150-0.

    Article  PubMed  CAS  Google Scholar 

  27. Jendrossek V, Grassmé H, Mueller I, Lang F, Gulbins E. Pseudomonas aeruginosa-induced apoptosis involves mitochondria and stress-activated protein kinases. Infect Immun. 2001;69:2675–2683. doi:10.1128/IAI.69.4.2675-2683.2001.

    Article  PubMed  CAS  Google Scholar 

  28. Jia J, Wang Y, Zhou L, Jin S. Expression of Pseudomonas aeruginosa toxin ExoS effectively induces apoptosis in host cells. Infect Immun. 2006;74:6557–6570. doi:10.1128/IAI.00591-06.

    Article  PubMed  CAS  Google Scholar 

  29. Jenkins CE, Swiatoniowski A, Power MR, Lin TJ. Pseudomonas aeruginosa-induced human mast cell apoptosis is associated with up-regulation of endogenous Bcl-xS and down-regulation of Bcl-xL. J Immunol. 2006;177:8000–8007.

    PubMed  CAS  Google Scholar 

  30. Castañeda F, Kinne RK. Apoptosis induced in HepG2 cells by short exposure to millimolar concentrations of ethanol involves the Fas-receptor pathway. J Cancer Res Clin Oncol. 2001;127:418–424. doi:10.1007/s004320000227.

    Article  PubMed  Google Scholar 

  31. Khan TH, Sultana S. Apigenin induces apoptosis in Hep G2 cells: possible role of TNF-alpha and IFN-gamma. Toxicology. 2006;217:206–212. doi:10.1016/j.tox.2005.09.019.

    Article  PubMed  CAS  Google Scholar 

  32. Hu QY, Li JN, Song DQ, et al. Inhibition of human hepatocellular carcinoma by l-proline-m-bis (2-chloroethyl) amino-l-phenylalanyl-l-norvaline ethyl ester hydrochloride (MF13) in vitro and in vivo. Int J Oncol. 2004;25:1289–1296.

    PubMed  CAS  Google Scholar 

  33. Xie SQ, Wu YL, Cheng PF, et al. A novel homospermidine conjugate inhibits growth and induces apoptosis in human hepatoma cells. Acta Pharmacol Sin. 2007;28:1827–1834. doi:10.1111/j.1745-7254.2007.00639.x.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This research was supported by a project of international cooperation (No. WB07C04).

Author information

Authors and Affiliations

  1. Department of Intervention, The First Affiliated Clinic College of Harbin Medical University, Harbin, Heilongjiang, China

    Zhenyuan Cao

  2. Department of Gastroenterology, The First Affiliated Clinic College of Harbin Medical University, Harbin, Heilongjiang, China

    Lijun Shi

  3. Department of Oncology, The First Affiliated Clinic College of Harbin Medical University, Harbin, Heilongjiang, China

    Ying Li

  4. Department of Neurobiology, Harbin Medical University Provincial Key Lab of Neurobiology, Harbin Medical University, Harbin, Heilongjiang, 150081, China

    Zhenyuan Cao, Jinghua Wang, Dandan Wang, Guangyou Wang, Bo Sun, Lili Mu & Hulun Li

  5. Homejoy Pharmaceuticals Company Limited, Shanghai, China

    Mingfei Yang

Authors
  1. Zhenyuan Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lijun Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ying Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jinghua Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dandan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Guangyou Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Bo Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Lili Mu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Mingfei Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Hulun Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hulun Li.

Additional information

Zhenyuan Cao, Lijun Shi, and Ying Li contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cao, Z., Shi, L., Li, Y. et al. Pseudomonas aeruginosa: Mannose Sensitive Hemagglutinin Inhibits the Growth of Human Hepatocarcinoma Cells via Mannose-Mediated Apoptosis. Dig Dis Sci 54, 2118–2127 (2009). https://doi.org/10.1007/s10620-008-0603-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-008-0603-5

Keywords

Search

Navigation