SpringerLink
Log in

Anticancer activity of Helicobacter pylori ribosomal protein (HPRP) with iRGD in treatment of colon cancer

  • Original Article – Cancer Research
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

As the conventional therapeutic approaches were not completely successful in the treatment of colon cancer, there is still a need for finding the most efficient therapeutic agents. Here we investigated the anticancer activity of HPRP-A1 that was derived from the N-terminal region of Helicobacter pylori ribosomal protein L1 (RpL1) alone or in combination with tumor-homing peptide iRGD and 5-Fluorouracil (5FU) on colon cancer cell lines (CT26 and HT29) and isograft models of colon cancer.

Method

We assessed the tumor growth inhibitory activity of HPRP-A1 with or without iRGD and 5FU on colon cancer in vitro and in vivo. In the in vitro part, we investigate the effect of HPRP-A1 alone and in combination with iRGD/5FU.

Results

Our results demonstrated that co-administration of HPRP-A1 with iRGD increased the apoptosis, while these two peptides in combination with 5FU increased the intracellular level of p53 that upregulate the pro-apoptotic gene BAX and downregulate the anti-apoptotic gene BCL2. HPRP-A1 blocks the cell cycle progression in G0/G1. Co-administration of two peptides significantly reduced the size and weight of the tumors, while the group that received 5FU in combination with the peptides increased the necrotic and decrease the fibrotic area significantly in the tumor tissues, which also disrupt the oxidant/antioxidant balance.

Conclusions

Our results indicated that HPRP-A1 could be considered an effective agent toward colon cancer in vitro and in vivo with the ability to enhance the effects of conventional chemotherapy agent 5FU.

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
EUR 32.99 /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 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
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  • Abedizadeh R, Rezvan H, Nourian A (2020) A new in vivo model for analysis of colon carcinoma micrometastasis in BALB/c mice. J Shahrekord Univ Med Sci 22(2):88–95

    Article  Google Scholar 

  • Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126

    Article  CAS  PubMed  Google Scholar 

  • Amerizadeh F, Rezaei N, Rahmani F, Hassanian SM, Moradi-Marjaneh R, Fiuji H et al (2018) Crocin synergistically enhances the antiproliferative activity of 5-flurouracil through Wnt/PI3K pathway in a mouse model of colitis-associated colorectal cancer. J Cell Biochem 119(12):10250

    Article  CAS  PubMed  Google Scholar 

  • Boohaker RJ, Lee M, Vishnubhotla P, Perez JLM, Khaled AR (2012) The use of therapeutic peptides to target and to kill cancer cells. Curr Med Chem 19(22):3794–3804

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cao C, Yan TD, Black D, Morris DL (2009) A systematic review and meta-analysis of cytoreductive surgery with perioperative intraperitoneal chemotherapy for peritoneal carcinomatosis of colorectal origin. Ann Surg Oncol 16(8):2152–2165

    Article  PubMed  Google Scholar 

  • Chang J, Liu Y, Han B, Zhou C, Bai C, Li J (2015) Pseudomonas aeruginosa preparation plus chemotherapy for advanced non-small-cell lung cancer: a randomized, multicenter, double-blind phase III study. Med Oncol 32(5):139

    Article  PubMed  CAS  Google Scholar 

  • Cohen E, Ophir I, Shaul YB (1999) Induced differentiation in HT29, a human colon adenocarcinoma cell line. J Cell Sci 112(16):2657–2666

    Article  CAS  PubMed  Google Scholar 

  • Dinarvand P, Hassanian SM, Weiler H, Rezaie AR (2015) Intraperitoneal administration of activated protein C prevents postsurgical adhesion band formation. Blood 125(8):1339–1348

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Elmi S, Sallam NA, Rahman MM, Teng X, Hunter AL, Moien-Afshari F et al (2008) Sulfaphenazole treatment restores endothelium-dependent vasodilation in diabetic mice. Vascul Pharmacol 48(1):1–8

    Article  CAS  PubMed  Google Scholar 

  • Fujimori M (2006) Genetically engineered bifidobacterium as a drug delivery system for systemic therapy of metastatic breast cancer patients. Breast Cancer 13(1):27–31

    Article  PubMed  Google Scholar 

  • Giovannetti E, Wang Q, Avan A, Funel N, Lagerweij T, Lee JH et al (2014) Role of CYB5A in pancreatic cancer prognosis and autophagy modulation. J Natl Cancer Inst 106(1):djt346

    Article  PubMed  CAS  Google Scholar 

  • Gontero P, Bohle A, Malmstrom P-U, O’Donnell MA, Oderda M, Sylvester R et al (2010) The role of bacillus Calmette-Guérin in the treatment of non–muscle-invasive bladder cancer. Eur Urol 57(3):410–429

    Article  PubMed  Google Scholar 

  • Gupta PK, Tripathi D, Kulkarni S, Rajan M (2016) Mycobacterium tuberculosis H37Rv infected THP-1 cells induce epithelial mesenchymal transition (EMT) in lung adenocarcinoma epithelial cell line (A549). Cell Immunol 300:33–40

    Article  CAS  PubMed  Google Scholar 

  • Haabeth OAW, Lorvik KB, Hammarström C, Donaldson IM, Haraldsen G, Bogen B et al (2011) Inflammation driven by tumour-specific Th1 cells protects against B-cell cancer. Nat Commun 2(1):1–12

    Article  CAS  Google Scholar 

  • Haabeth OAW, Lorvik KB, Yagita H, Bogen B, Corthay A (2016) Interleukin-1 is required for cancer eradication mediated by tumor-specific Th1 cells. Oncoimmunology 5(1):e1039763

    Article  PubMed  CAS  Google Scholar 

  • Hamilton AM, Aidoudi-Ahmed S, Sharma S, Kotamraju VR, Foster PJ, Sugahara KN et al (2015) Nanoparticles coated with the tumor-penetrating peptide iRGD reduce experimental breast cancer metastasis in the brain. J Mol Med 93(9):991–1001

    Article  CAS  PubMed  Google Scholar 

  • Han E-S, Muller FL, Pérez VI, Qi W, Liang H, ** L et al (2008) The in vivo gene expression signature of oxidative stress. Physiol Genomics 34(1):112–126

    Article  CAS  PubMed  Google Scholar 

  • Hao X, Yan Q, Zhao J, Wang W, Huang Y, Chen Y (2015) TAT modification of alpha-helical anticancer peptides to improve specificity and efficacy. PLoS ONE 10(9):e0138911

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hao W, Hu C, Huang Y, Chen Y (2019) Coadministration of kla peptide with HPRP-A1 to enhance anticancer activity. PLoS ONE 14(11):e0223738

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hetz C, Bono MR, Barros LF, Lagos R (2002) Microcin E492, a channel-forming bacteriocin from Klebsiella pneumoniae, induces apoptosis in some human cell lines. Proc Natl Acad Sci 99(5):2696–2701

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hu C, Chen X, Huang Y, Chen Y (2018a) Co-administration of iRGD with peptide HPRP-A1 to improve anticancer activity and membrane penetrability. Sci Rep 8(1):2274

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hu C, Huang Y, Chen Y (2018b) Targeted modification of the cationic anticancer peptide HPRP-A1 with iRGD to improve specificity, penetration, and tumor-tissue accumulation. Mol Pharm 16(2):561–572

    Article  CAS  Google Scholar 

  • Hu C, Chen X, Huang Y, Chen Y (2018c) Synergistic effect of the pro-apoptosis peptide kla-TAT and the cationic anticancer peptide HPRP-A1. Apoptosis 23(2):132–142

    Article  CAS  PubMed  Google Scholar 

  • Hu C, Chen X, Huang Y, Chen Y (2018d) Co-administration of iRGD with peptide HPRP-A1 to improve anticancer activity and membrane penetrability. Sci Rep 8(1):1–14

    CAS  Google Scholar 

  • Kang H-L, Lee W-K, Song J-Y, Choi S-H, Park S-G, Ryu B-D et al (2005) Helicobacter pylori Strain 51 (Korean Isolate): ordered overlap** BAC Library, combined physical and genetic map, and comparative analysis with H. pylori strain 26695 and strain J99. J Microbiol Biotechnol 15(4):844–854

    CAS  Google Scholar 

  • Kuwana T, Bouchier-Hayes L, Chipuk JE, Bonzon C, Sullivan BA, Green DR et al (2005) BH3 domains of BH3-only proteins differentially regulate Bax-mediated mitochondrial membrane permeabilization both directly and indirectly. Mol Cell 17(4):525–535

    Article  CAS  PubMed  Google Scholar 

  • Lax AJ (2005) Bacterial toxins and cancer—a case to answer? Nat Rev Microbiol 3(4):343

    Article  CAS  PubMed  Google Scholar 

  • Lecuit M, Abachin E, Martin A, Poyart C, Pochart P, Suarez F et al (2004) Immunoproliferative small intestinal disease associated with Campylobacter jejuni. N Engl J Med 350(3):239–248

    Article  CAS  PubMed  Google Scholar 

  • Lemoine L, Sugarbaker P, Van der Speeten K (2016) Pathophysiology of colorectal peritoneal carcinomatosis: role of the peritoneum. World J Gastroenterol 22(34):7692

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marjaneh RM, Rahmani F, Hassanian SM, Rezaei N, Hashemzehi M, Bahrami A et al (2018) Phytosomal curcumin inhibits tumor growth in colitis-associated colorectal cancer. J Cell Physiol 233(10):6785–6798

    Article  CAS  PubMed  Google Scholar 

  • Marqus S, Pirogova E, Piva TJ (2017) Evaluation of the use of therapeutic peptides for cancer treatment. J Biomed Sci 24(1):21

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Nath G, Gulati AK, Shukla VK (2010) Role of bacteria in carcinogenesis, with special reference to carcinoma of the gallbladder. World J Gastroenterol: WJG 16(43):5395

    Article  PubMed  PubMed Central  Google Scholar 

  • Nautiyal J, Kanwar SS, Yu Y, Majumdar AP (2011) Combination of dasatinib and curcumin eliminates chemo-resistant colon cancer cells. J Mol Signal 6(1):1–11

    Google Scholar 

  • Pütsep K, Brändén C-I, Boman HG, Normark S (1999) Antibacterial peptide from H. pylori. Nature 398(6729):671

    Article  PubMed  Google Scholar 

  • Qifan W, Fen N, Ying X, **nwei F, Jun D, Ge Z (2016) iRGD-targeted delivery of a pro-apoptotic peptide activated by cathepsin B inhibits tumor growth and metastasis in mice. Tumor Biol 37(8):10643–10652

    Article  CAS  Google Scholar 

  • Roberts NJ, Zhang L, Janku F, Collins A, Bai R-Y, Staedtke V et al (2014) Intratumoral injection of clostridium novyi-NT spores induces antitumor responses. Sci Transl Med 6(249):249ra111-249ra111

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ruoslahti E (2017) Tumor penetrating peptides for improved drug delivery. Adv Drug Deliv Rev 110:3–12

    Article  PubMed  CAS  Google Scholar 

  • Shin K, Lee J, Guo N, Kim J, Lim A, Qu L et al (2011) Hedgehog/Wnt feedback supports regenerative proliferation of epithelial stem cells in bladder. Nature 472(7341):110–114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shin K, Lim A, Zhao C, Sahoo D, Pan Y, Spiekerkoetter E et al (2014) Hedgehog signaling restrains bladder cancer progression by eliciting stromal production of urothelial differentiation factors. Cancer Cell 26(4):521–533

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Siegel RL, Miller KD, Jemal A (2020) Cancer statistics, 2020. CA: Cancer J Clin 70(1):7–30

    Google Scholar 

  • Sugahara KN, Teesalu T, Karmali PP, Kotamraju VR, Agemy L, Girard OM et al (2009) Tissue-penetrating delivery of compounds and nanoparticles into tumors. Cancer Cell 16(6):510–520

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sugahara KNTT, Karmali PP, Kotamraju VR, Agemy L, Greenwald DR, Ruoslahti E (2010) Coadministration of a tumor-penetrating peptide enhances the efficacy of cancer drugs. Science 328(5981):1031–1035

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sugarbaker PH (2016) Improving oncologic outcomes for colorectal cancer at high risk for local–regional recurrence with novel surgical techniques. Expert Rev Gastroenterol Hepatol 10(2):205–213

    Article  CAS  PubMed  Google Scholar 

  • Teesalu TSK, Kotamraju VR, Ruoslahti E (2009) C-end rule peptides mediate neuropilin-1-dependent cell, vascular, and tissue penetration. PNAS 106(38):16157–16162

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Teesalu T, Sugahara KN, Ruoslahti E (2013) Tumor-penetrating peptides. Front Oncol 3:216

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang J-L, Liu D, Zhang Z-J, Shan S, Han X, Srinivasula SM et al (2000) Structure-based discovery of an organic compound that binds Bcl-2 protein and induces apoptosis of tumor cells. Proc Natl Acad Sci 97(13):7124–7129

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wei MQ, Ellem KA, Dunn P, West MJ, Bai CX, Vogelstein B (2007) Facultative or obligate anaerobic bacteria have the potential for multimodality therapy of solid tumours. Eur J Cancer 43(3):490–496

    Article  PubMed  Google Scholar 

  • Yan L, Kanada M, Zhang J, Okazaki S, Terakawa S (2015) Photodynamic treatment of tumor with bacteria expressing killerred. PLoS ONE 10(7):e0131518

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhang Y, Davis C, Ryan J, Janney C, Peña MMO (2013) Development and characterization of a reliable mouse model of colorectal cancer metastasis to the liver. Clin Exp Metas 30(7):903–918

    Article  CAS  Google Scholar 

  • Zhao M, Yang M, Ma H, Li X, Tan X, Li S et al (2006) Targeted therapy with a Salmonella typhimurium leucine-arginine auxotroph cures orthotopic human breast tumors in nude mice. Can Res 66(15):7647–7652

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was a part of a Ph.D. dissertation by Atieh Yaghoubi.

Funding

This research was funded by Mashhad University of Medical Sciences, Mashhad, Iran (981262).

Author information

Author notes

  1. Atieh Yaghoubi and Fereshteh Asgharzadeh contributed equally to this work.

Authors and Affiliations

  1. Antimicrobial Resistance Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran

    Atieh Yaghoubi, Aref Movaqar, Kiarash Ghazvini & Saman Soleimanpour

  2. Department of Microbiology and Virology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Atieh Yaghoubi, Aref Movaqar, Kiarash Ghazvini & Saman Soleimanpour

  3. Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Fereshteh Asgharzadeh & Majid Khazaei

  4. Department of Medical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Seyed Mahdi Hassanian

  5. Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Amir Avan

  6. Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Seyed Mahdi Hassanian, Amir Avan, Majid Khazaei & Saman Soleimanpour

Authors
  1. Atieh Yaghoubi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fereshteh Asgharzadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Aref Movaqar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kiarash Ghazvini
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Seyed Mahdi Hassanian
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Amir Avan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Majid Khazaei
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Saman Soleimanpour
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Majid Khazaei or Saman Soleimanpour.

Ethics declarations

Conflict of interest

The authors have declared that have no conflict of interest.

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

Yaghoubi, A., Asgharzadeh, F., Movaqar, A. et al. Anticancer activity of Helicobacter pylori ribosomal protein (HPRP) with iRGD in treatment of colon cancer. J Cancer Res Clin Oncol 147, 2851–2865 (2021). https://doi.org/10.1007/s00432-021-03683-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-021-03683-7

Keywords

Search

Navigation