Anti-cancer peptides from bacteria

  • Tomasz M. Karpinski Department of Medical Microbiology, Poznan University of Medical Sciences
  • Anna K. Szkaradkiewicz Department of Conservative Dentistry and Periodontology, Poznan University of Medical Sciences
Keywords: anticancer peptides, bacteria, apoptosis, toxins, azurin, Entap


Cancer is a leading cause of death in the world. The rapid development of medicine and pharmacology allows to create new and effective anticancer drugs. Among modern anticancer drugs are bacterial proteins. Until now has been shown anticancer activity among others azurin and exotoxin A from Pseudomonas aeruginosa, Pep27anal2 from Streptococcus pneumoniae, diphtheria toxin from Corynebacterium diphtheriae, and recently discovered Entap from Enterococcus sp. The study presents the current data regarding the properties, action and anticancer activity of listed peptides.


Download data is not yet available.
2295 Read


Adman ET. Copper protein structures. Adv Protein Chem. 1991; 42: 145-97.

Alexandroff AB, Jackson AM, O'Donnell MA, James K. BCG immunotherapy of bladder cancer: 20 years on. Lancet 1999; 353: 1689-94.

Apiyo D, Wittung-Stafshede P. Unique complex between bacterial azurin and tumor-suppressor protein p53. Biochem Biophys Res Commun. 2005; 332: 965-68.

Bacha P, Williams DP, Waters C, et al. Interleukin 2 receptor-targeted cytotoxicity. Interleukin 2 receptor-mediated action of a diphtheria toxin-related interleukin 2 fusion protein. J Exp Med. 1988; 167: 612-22.

Bernardes N, Chakrabarty AM, Fialho AM. Engineering of bacterial strains and their products for cancer therapy. Appl Microbiol Biotechnol. 2013; 97: 5189-99.

Carswell EA, Old LJ, Kassel RL, et al. An endotoxin induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci USA. 1975; 72: 3666-70.

Choi J-H, Lee M-H, Cho Y-J, et al. The bacterial protein Azurin enhances sensitivity of oral squamous carcinoma cells to anticancer drugs. Yonsei Med J. 2011; 52: 773-78.

Coley WB. The treatment of inoperable sarcoma by bacterial toxins (the mixed toxins of the Streptococcus erysipelatis and Bacillus prodigiosus). Proc R Soc Med Surg. 1909; 3: 1-48.

Dang LH, Bettegowda C, Huso DL, et al. Combination bacteriolytic therapy for the treatment of experimental tumors. Proc Natl Acad Sci USA. 2001; 98: 15155-60.

De Jong MC, Scheffer GL, Broxterman HJ, et al. Multidrug-resistant tumor cells remain sensitive to a recombinant interleukin-4-Pseudomonas exotoxin, except when overexpressing the multidrug resistance protein MRP1. Clin Cancer Res. 2003; 9: 5009-17.

Duvic M, Geskin L, Prince HM. Duration of response in cutaneous T-cell lymphoma patients treated with denileukin diftitox: results from 3 Phase III studies. Clin Lymphoma Myeloma Leuk. 2013: S2152-2650(13)00095-5.

Gorman GS, Coward LU, Freeman L, et al. A novel and rapid LC/MS/MS assay for bioanalysis of Azurin p28 in serum and its pharmacokinetics in mice. J Pharm Biomed Anal. 2010; 53: 991-96.

Goto M, Yamada T, Kimbara K, et al. Induction of apoptosis in macrophages by Pseudomonas aeruginosa azurin: tumour-suppressor protein p53 and reactive oxygen species, but not redox activity, as critical elements in cytotoxicity. Mol Microbiol. 2003; 47: 549-59.

Gratia A, Linz R. Le phénoméne de Schwartzmann dans le sarcome du Cobaye. C R Séances Soc Biol Paris 1931; 108: 427-28.

Holmes RK. Biology and molecular epidemiology of diphtheria toxin and the tox gene. J Infect Dis. 2000; 181 Suppl 1: S156-67.

Huang Y-B, Wang X-F, Wang H-Y. Studies on mechanism of action of anticancer peptides by modulation of hydrophobicity within a defined structural framework. Mol Cancer Ther. 2011; 10: 416-26.

Jia L, Gorman GS, Coward LU, et al. Preclinical pharmacokinetics, metabolism, and toxicity of azurin-p28 (NSC745104) a peptide inhibitor of p53 ubiquitination. Cancer Chemother Pharmacol. 2011; 68: 513-24.

Karpi?ski TM. New peptide (Entap) with anti-proliferative activity produced by bacteria of Enterococcus genus (in Polish). Habilitation thesis. Scientific Publisher of Pozna? University of Medical Sciences, 2012.

Karpinski TM, Szkaradkiewicz A, Gamian A. New enterococcal anticancer peptide. 23rd European Congress of Clinical Microbiology and Infectious Diseases. Berlin, Germany, 27-30 April 2013. Program and Abstracts. 2013, p 1661.

Kiefer F, Arnold K, Künzli M, Bordoli L, Schwede T. The SWISS-MODEL Repository and associated resources. Nucleic Acids Res. 2009; 37: D387-92.

Kunami N, Yotsumoto F, Ishitsuka K, et al. Antitumor effects of CRM197, a specific inhibitor of HB-EGF, in T-cell acute lymphoblastic leukemia. Anticancer Res. 2011; 31: 2483-88.

Laske DW, Youle RJ, Oldfield EH. Tumor regression with regional distribution of the targeted toxin TF-CRM107 in patients with malignant brain tumors. Nat Med. 1997; 3: 1362-68.

Lee DG, Hahm K-S, Park Y, et al. Functional and structural characteristics of anticancer peptide Pep27 analogues. Cancer Cell Int. 2005; 5: 21.

Martarelli D, Pompei P, Mazzoni G. Inhibition of adrenocortical carcinoma by diphtheria toxin mutant CRM197. Chemotherapy. 2009; 55: 425-32.

Mehta RR, Yamada T, Taylor BN, et al. A cell penetrating peptide derived from azurin inhibits angiogenesis and tumor growth by inhibiting phosphorylation of VEGFR-2, FAK and Akt. Angiogenesis 2011; 14: 355-69.

Murphy JR. Mechanism of diphtheria toxin catalytic domain delivery to the eukaryotic cell cytosol and the cellular factors that directly participate in the process. Toxins (Basel). 2011; 3: 294-308.

Nar H, Messerschmidt A, Huber R, et al. Crystal structure of Pseudomonas aeruginosa apoazurin at 1.85 Å resolution. FEBS Lett. 1992; 306: 119-24.

Oh S, Todhunter DA, Panoskaltsis-Mortari A, et al. A deimmunized bispecific ligand-directed toxin that shows an impressive anti-pancreatic cancer effect in a systemic nude mouse orthotopic model. Pancreas 2012; 41: 789-96.

Patyar S, Joshi R, Prasad Byrav DS, et al. Bacteria in cancer therapy: A novel experimental strategy. J Biomed Sci. 2010; 17: 21.

Pawelek J, Low K, Bermudes D. Tumor-targeted Salmonella as a novel anticancer vector. Cancer Res. 1997; 57: 4537-44.

Punj V, Bhattacharyya S, Saint-Dic D, et al. Bacterial cupredoxin azurin as an inducer of apoptosis and regression in human breast cancer. Oncogene. 2004; 23: 2367-78.

Risberg K, Fodstad O, Andersson Y. Synergistic anticancer effects of the 9.2.27PE immunotoxin and ABT-737 in melanoma. PLoS One. 2011; 6: e24012.

Sung WS, Park Y, Choi CH, et al. Mode of antibacterial action of a signal peptide, Pep27 from Streptococcus pneumoniae. Biochem Biophys Res Commun. 2007; 363: 806-10.

Szkaradkiewicz A, Karpinski TM, Gamian A, et al. Identification of carcinoma suppressive factor produced by bacteria of Enterococcus genus. Clin Microbiol Infect 2012; 18, s3: 355, p1366.

Taranta M, Bizzarri AR, Cannistraro S. Probing the interaction between p53 and the bacterial protein azurin by single molecule force spectroscopy. J Mol Recognit 2008; 21: 63-70.

Vallera DA, Li C, Jin N, et al. Targeting urokinase-type plasminogen activator receptor on human glioblastoma tumors with diphtheria toxin fusion protein DTAT. J Natl Cancer Inst. 2002; 94: 597-606.

van de Kamp M, Silvestrini MC, Brunori M, et al. Involvement of the hydrophobic patch of azurin in the electron-transfer reactions with cytochrome c551 and nitrite reductase. Eur J Biochem. 1990; 194: 109-18.

Vasu P, Bhattacharyya S, Saint-Dic D, et al. Bacterial cupredoxin azurin as an inducer of apoptosis and regression in human breast cancer. Oncogene 2004; 23: 2367-78.

Waldron NN, Kaufman DS, Oh S, et al. Targeting tumor-initiating cancer cells with dCD133KDEL shows impressive tumor reductions in a xenotransplant model of human head and neck cancer. Mol Cancer Ther. 2011; 10: 1829-38.

Wang L, Wang P, Liu Y, Xue Y. Regulation of cellular growth, apoptosis, and Akt activity in human U251 glioma cells by a combination of cisplatin with CRM197. Anticancer Drugs 2012; 23: 81-89.

Wolf P, Elsasser-Beile U. Pseudomonas exotoxin A-based immunotoxins for targeted cancer therapy. In: Emerging cancer therapy: Microbial approaches and biotechnological tools. Fialho AM, Chakrabarty AM (eds). John Wiley and Sons, 2010.

Yamada T, Goto M, Punj V, et al. Bacterial redox protein azurin, tumor suppressor protein p53, and regression of cancer. PNAS 2002a; 99: 14098-103.

Yamada T, Goto M, Punj V, et al. The bacterial redox protein azurin induces apoptosis in J774 macrophages through complex formation and stabilization of the tumor suppressor protein p53. Infect Immun. 2002b; 70: 7054-62.

Yamada T, Hiraoka Y, Ikehata M, et al. Apoptosis or growth arrest: Modulation of tumor suppressor p53's specificity by bacterial redox protein azurin. Proc Natl Acad Sci USA. 2004; 101: 4770-75.

Yamada T, Mehta RR, Lekmine F, et al. A peptide fragment of azurin induces a p53-mediated cell cycle arrest in human breast cancer cells. Mol Cancer Ther. 2009; 8: 2947-58.

How to Cite
Karpinski, T., and A. Szkaradkiewicz. “Anti-Cancer Peptides from Bacteria”. Bangladesh Journal of Pharmacology, Vol. 8, no. 3, Aug. 2013, pp. 343-8, doi:10.3329/bjp.v8i3.15704.
Mini Review