Skip to main content
Log in

Newly isolated marine bacterial exopolysaccharides enhance antitumor activity in HepG2 cells via affecting key apoptotic factors and activating toll like receptors

  • Original Article
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Hepatocellular carcinoma (HCC) was accompanied by high incidence of morbidity and mortality worldwide. Apoptosis is a vital biological process playing a critical role in cancer. Besides, toll like receptors were reported to regulator the innate immune response against cancer development. Exopolysaccharides (EPSs) derived from marine bacteria were reported to have a potential biological importance. This work aimed to elucidate the antitumor effects of newly isolated EPSs against HepG2 cells. Moreover, their effects on some apoptotic markers and TLRs were followed. Isolated EPSs were tested for their cytotoxic effects in a previous study and the most promising; MSA1, E4, MGA2, SGA3, and NRC7 EPSs were subjected to molecular analysis to investigate their pro-apoptotic effects, in addition to their effects on TLR2 and TLR-9 using quantitative real time RT-PCR. And the most cytotoxic and pro-apoptotic EPS; MSA1 were subjected to antibody array analysis to investigate a panel of 43 apoptotic proteins. All isolated EPSs produced a positive role in regulating the apoptotic gene and increasing the TLRs expression in different manners. However, the most promising EPS was MSA1. It showed pro-apoptotic effects on gene and protein levels, besides its up-regulation of TLRs.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Pistritto G, Trisciuoglio D, Ceci C, Garufi A, D’Orazi G (2016) Apoptosis as anticancer mechanism: function and dysfunction of its modulators and targeted therapeutic strategies. Aging 8(4):603–619

    Article  CAS  Google Scholar 

  2. Plati J, Bucur O, Khosravi-Far R (2008) Dysregulation of apoptotic signaling in cancer. Molecular mechanisms and therapeutic opportunities. J Cell Biochem 104:1124–1149

    Article  CAS  Google Scholar 

  3. Fulda S (2009) Tumor resistance to apoptosis. Int J Cancer 124:515

    Article  Google Scholar 

  4. Tsujimoto Y, Cossman E, Croce C (1985) Involvement of the BCL-2 gene in human follicular lymphomas. Science 228:1440

    Article  CAS  Google Scholar 

  5. Dajon M, Iribarren K, Cremer I (2016) Toll-like receptor stimulation in cancer: a pro- and anti-tumor double-edged sword. Immunobiology S0171–2985(16):30096. https://doi.org/10.1016/j.imbio.2016.06.009

    Article  CAS  Google Scholar 

  6. Asker MS, El Sayed OH, Mahmoud MG, Yahya SM, Mohamed SS, Selim MS, El Awady MS, Abdelnasser SM, Abo Elsoud MM (2018) Production of exopolysaccharides from novel marine bacteria and anticancer activity against hepatocellular carcinoma cells (HepG2). Bull Natl Res Cent 42:30

    Article  Google Scholar 

  7. https://www.qiagen.com/us/products/discovery-and-translational-research/lab-essentials/buffers-reagents/qiazol-lysis-reagent/#orderinginformation

  8. https://www.qiagen.com/us/products/discovery-and-translational-research/pcr-qpcr/real-time-pcr-enzymes-and-kits/sybr-green-or-dye-based-one-step-qrt-pcr/ quantifast-sybr-green-rt-pcr- it/#orderinginformation

  9. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein- Dye binding. Anal Biochem 72:248–254

    Article  CAS  Google Scholar 

  10. https://www.qiagen.com/us/products/discovery-and-translational-research/pcr-qpcr/real-time-pcr-enzymes-and-kits/sybr-green-or-dye-based-one-step-qrt-pcr/quantifast-sybr-green-rt-pcr-kit/#orderinginformation

  11. https://reactome.org/PathwayBrowser/#TOOL=AT

  12. Charo J, Finkelstein SE, Grewal N, Restifo NP, Robbins PF, Rosenberg SA (2008) BCL-2 over expression enhances tumor-specific T cell survival. Cancer Res 65:2001–2008

    Article  Google Scholar 

  13. Zuzak TJ, Steinhoff DF, Sutton LN, Phillips PC, Eggert A, Grotzer MA (2002) Loss of caspase-8 mRNA expression is common in childhood primitive neuroectodermal brain tumor/medulloblastoma. Eur J Cancer 38:83–91

    Article  CAS  Google Scholar 

  14. Vousden KH (2000) P53: death star. Cell 103:691–694

    Article  CAS  Google Scholar 

  15. Benne M, Macdonald K, Chan SW, Luzio JP, Simari R, Weissberg P (1998) Cell surface trafficking of Fas: a rapid mechanisms of p53-mediated apoptosis. Science 282:290–293

    Article  Google Scholar 

  16. Westphal D, Dewson G, Czabotar PE, Kluck RM (2011) Molecular biology of Bax and Bak activation and action. Biochim Biophys Acta 1813:521–553

    Article  CAS  Google Scholar 

  17. Thomberry NA, Laxebnik Y (1998) Caspases: enemies within. Science 281:1312–1316

    Article  Google Scholar 

  18. Stennicke HR, Salvesen GS (2000) Caspases–controlling intracellular signals by protease zymogen activation. Biochim Biophys Acta Port Struct Mol Enzimol. 1477:299–306

    Article  CAS  Google Scholar 

  19. Heath AW, Chang R, Harada N et al (1993) Antibodies to murine CD40 stimulate normal B lymphocytes but inhibit proliferation of B lymphoma cells. Cell Immunol 152:468–480

    Article  CAS  Google Scholar 

  20. Hanyu K, Iiida T, Shiba H, Ohashi T, Eto Y, Yanaga K (2008) Immunogene therapy by adenovirus vector expressing Cd40ligand for metastatic liver cancer in rats. Anticancer Res 28:2785–2790

    PubMed  Google Scholar 

  21. Qi Y, Xia P (2012) Cellular inhibitor of apoptosis protein-1(cIAP1) plays a critical role in -cell survival under endoplasmic reticulum stress: promoting ubiquttnatin and degradation of C/EBP homologus protein (CHOP)*. Biol Chem 287(38):32236–32245

    Article  CAS  Google Scholar 

  22. Gao W, Pu W, Luo KQ, Chang DC (2012) Temporal relationship between cytochrome c releaseand mitochondrial swelling during UV-induced apoptosis in living HeLa cells. J Biol Chem 287(38):32236–32245

    Article  Google Scholar 

  23. Yang X, Shi B, Li L, Xu Z, Ge Y, Shi J, Liu Y, Zheng D (2016) Death receptor 6 (DR6) is required for mouse B16 tumorangiogenesis via the NF-κB, P38 MAPK and STAT3 pathways. Oncogenesis 5:e206. https://doi.org/10.1038/oncsis.2016.9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Di O, Nally K, Kelly RG, O’Connor TM, Shanahan F, O’Connell J (2005) Targeting the Fas/Fas ligand pathway in cancer. Expert Opin Ther Targets 9(5):1031–1044

    Article  Google Scholar 

  25. Kottke T, Sanchez-Perez L, Diaz RM, Thompson J, Chong H, Harrington K, Calderwood SK, Pulido J, Georgopoulos N, Selby P, Melcher A, Vile R (2007) Induction of hsp70-mediated Th17autoimmunity can be exploitedas immunotherapy for metastaticprostate cancer. Cancer Res 67:11970–11979

    Article  CAS  Google Scholar 

  26. Zurawa-Janicka D, Skorko-Glonek J, Lipinska B (2010) HtrA proteins as targets in therapy of cancer and other diseases. Expert Opin Ther Targets 14(7):665–679

    Article  CAS  Google Scholar 

  27. Varsha P, Prasanna BC, Atreya HS (2015) Insulin-like growth factor system in cancer: novel targeted therapies. Res Int. https://doi.org/10.1155/2015/538019

    Article  Google Scholar 

  28. Elmegeed GA, Yahya SMM, Abd-Elhalim MM, Mohamed MS, Mohareb RM, Elsayed GH (2016) Evaluation of heterocyclic steroids and curcumin derivatives as antibreast cancer agents: studying the effect on apoptosis in MCF-7 breast cancer cells. Steroids 115:80–89

    Article  CAS  Google Scholar 

  29. Yahya SMM, Abdelhamid AO, Abd-Elhalim MM, Elsayed GH, Eskander EF (2017) The effect of newly synthesized progesterone derivatives on apoptotic and angiogenic pathway in MCF-7 breast cancer cells. Steroids 126:15–23

    Article  CAS  Google Scholar 

  30. LaCasse EC, Mahoney DJ, Cheung HH, Plenchette S, Baird S, Korneluk RG (2008) IAP-targeted therapies for cancer. Oncogene 27:6252–6275

    Article  CAS  Google Scholar 

  31. Guicciardi ME, Gores GJ (2009) Life and death by death receptors. FASEB J 23:1625–1637

    Article  CAS  Google Scholar 

  32. Tukenmez U, Aktas B, Aslim B, Yavuz S (2019) The relationship between the structural characteristics of lactobacilli-EPS and its ability to induce apoptosis in colon cancer cells in vitro. Sci Rep. 9:8268. https://doi.org/10.1038/s41598-019-44753-8

    Article  CAS  PubMed Central  Google Scholar 

  33. Wang L, Wang Y, Li Q, Tian K, Xu L, Liu G, Guo C (2019) Exopolysaccharide, isolated from a novel strain Bifidobacterium breve lw01 possess an anticancer effect on head and neck cancer—genetic and biochemical evidences. Front Microbiol 10:1044. https://doi.org/10.3389/fmicb.2019.01044eCollection 2019

    Article  PubMed Central  Google Scholar 

  34. Di W, Zhang L, Yi H, Han X, Zhang Y, Xin L (2018) Exopolysaccharides produced by Lactobacillus strains suppress HT-29 cell growth via induction of G0/G1 cell cycle arrest and apoptosis. Oncol Lett. 16(3):3577–3586. https://doi.org/10.3892/ol.2018.9129Epub 2018 Jul 11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Fabregat A, Sidiropoulos K, Viteri G, Forner O, Marin-Garcia P, Arnau V, D’Eustachio P, Stein L, Hermjakob H (2017) Reactome pathway analysis: a high-performance in-memory approach. BMC Bioinform 18(1):142. https://doi.org/10.1186/s12859-017-1559-2

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was funded by the National Research Centre (Project number 10050306).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Shaymaa M.M. Yahya.

Ethics declarations

Conflict of interest

The authors declare that there are no conflicts of interests.

Research involving human and animal participants

This study does not involve human Participants or Animals.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yahya, S.M., Abdelnasser, S.M., Hamed, A.R. et al. Newly isolated marine bacterial exopolysaccharides enhance antitumor activity in HepG2 cells via affecting key apoptotic factors and activating toll like receptors. Mol Biol Rep 46, 6231–6241 (2019). https://doi.org/10.1007/s11033-019-05061-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-019-05061-6

Keywords

Navigation