Abstract
After breast cancer, gynecological cancer is the most prevalent type of cancer in female population. The most frequently diagnosed types of gynecological cancers are cervical and ovarian cancer. Since the conventional treatments of cancer were unsuccessful in complete treatment of malignancy and they faced limitations, there is a need for the development of new treatments. Among the new treatments, bacteriotherapy has attracted much attention due to its promising results. Bacteriotherapy means using bacteria strains or their different products in the treatment of cancer. The key advantage of bacteriotherapy in comparison to conventional therapy is the specific toxicity toward tumor cells. Moreover, living, attenuated, or genetically modified strains of bacteria are able to selectively target and internalize into the tumor cells, colonize and service within the hypoxic condition of the tumor, and finally lead to tumor suppression. The present study aimed to overview the current knowledge of using bacteria and their substances (including peptides, bacteriocins, spores, and toxins) in the treatment of different types of gynecological cancers.
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Abdi-Ali A, Worobec E, Deezagi A, Malekzadeh F (2004) Cytotoxic effects of pyocin S2 produced by Pseudomonas aeruginosa on the growth of three human cell lines. Can J Microbiol 50(5):375–381
Abraham SA, Waterhouse DN, Mayer LD, Cullis PR, Madden TD, Bally MB (2005) The liposomal formulation of doxorubicin. Methods Enzymol 391:71–97
Al-Zeer MA, Xavier A, Lubad MA, Sigulla J, Kessler M, Hurwitz R, Meyer TF (2017) Chlamydia trachomatis prevents apoptosis via activation of PDPK1-MYC and enhanced mitochondrial binding of hexokinase II. EBioMedicine 23:100–110
Appelberg R (2007) Neutrophils and intracellular pathogens: beyond phagocytosis and killing. Trends Microbiol 15(2):87–92
Audirac-Chalifour A, Torres-Poveda K, Bahena-Roman M, Tellez-Sosa J, Martinez-Barnetche J, Cortina-Ceballos B, Lopez-Estrada G, Delgado-Romero K, Burguete-Garcia AI, Cantu D (2016) Cervical microbiome and cytokine profile at various stages of cervical cancer: a pilot study. PLoS ONE. https://doi.org/10.1371/journal.pone.0153274
Avramis VI, Sencer S, Periclou AP, Sather H, Bostrom BC, Cohen LJ, Ettinger AG, Ettinger LJ, Franklin J, Gaynon PS (2002) A randomized comparison of native Escherichia coli asparaginase and polyethylene glycol conjugated asparaginase for treatment of children with newly diagnosed standard-risk acute lymphoblastic leukemia: a Children’s Cancer Group study. Blood 99(6):1986–1994
Baindara P, Gautam A, Raghava G, Korpole S (2017) Anticancer properties of a defensin like class IId bacteriocin Laterosporulin10. Sci Rep 7:46541
Baker JM, Chase DM, Herbst-Kralovetz MM (2018) Uterine microbiota: residents, tourists, or invaders? Front Immunol 9:208
Balgir PP, Bhatia P, Kaur B (2010) Sequence analysis and homology based modeling to assess structure-function relationship of pediocin CP2 of Pediococcus acidilactici MTCC 5101. Indian J Microtechnol 9:431–434
Black JD, Lopez S, Cocco E, Schwab CL, English DP, Santin AD (2015) Clostridium perfringens enterotoxin (CPE) and CPE-binding domain (c-CPE) for the detection and treatment of gynecologic cancers. Toxins 7(4):1116–1125
Borella F, Carosso AR, Cosma S, Preti M, Collemi G, Cassoni P, Bertero L, Benedetto C (2021) Gut microbiota and gynecological cancers: a summary of pathogenetic mechanisms and future directions. ACS Infect Dis 7(5):987–1009
Braundmeier AG, Lenz KM, Inman KS, Chia N, Jeraldo P, Walther-António MR, Berg Miller ME, Yang F, Creedon DJ, Nelson H (2015) Individualized medicine and the microbiome in reproductive tract. Front Physiol 6:97
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68(6):394–424
Cagel M, Grotz E, Bernabeu E, Moretton MA, Chiappetta DA (2017) Doxorubicin: nanotechnological overviews from bench to bedside. Drug Discov Today 22(2):270–281
Cameron A, Zaheer R, Adator EH, Barbieri R, Reuter T, McAllister TA (2019) Bacteriocin occurrence and activity in Escherichia coli isolated from bovines and wastewater. Toxins 11(8):475
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
Cascales E, Buchanan SK, Duché D, Kleanthous C, Lloubes R, Postle K, Riley M, Slatin S, Cavard D (2007) Colicin biology. Microbiol Mol Biol Rev 71(1):158–229
Chambers LM, Bussies P, Vargas R, Esakov E, Tewari S, Reizes O, Michener C (2021) The microbiome and gynecologic cancer: Current evidence and future opportunities. Curr Oncol Rep 23(8):1–12
Clairmont C, Lee K, Pike J, Ittensohn M, Low K, Pawelek J, Bermudes D, Brecher S, Margitich D, Turnier J (2000) Biodistribution and genetic stability of the novel antitumor agent VNP20009, a genetically modified strain of Salmonella typhimuvium. J Infect Dis 181(6):1996–2002
Danino T, Prindle A, Hasty J, Bhatia S (2013) Measuring growth and gene expression dynamics of tumor-targeted S. typhimurium bacteria. JoVE 77:e50540
Denny WA (2004) Tumor-activated prodrugs—a new approach to cancer therapy. Cancer Invest 22(4):604–619
DeSantis CE, Lin CC, Mariotto AB, Siegel RL, Stein KD, Kramer JL, Alteri R, Robbins AS, Jemal A (2014) Cancer treatment and survivorship statistics, 2014. CA Cancer J Clin 64(4):252–271
Deutscher SL (2010) Phage display in molecular imaging and diagnosis of cancer. Chem Rev 110(5):3196–3211
Ding L, Lu Z, Lu Q, Chen Y-H (2013) The claudin family of proteins in human malignancy: a clinical perspective. Cancer Manage Res 5:367
Egger C, Cannet C, Gérard C, Jarman E, Jarai G, Feige A, Suply T, Micard A, Dunbar A, Tigani B (2013) Administration of bleomycin via the oropharyngeal aspiration route leads to sustained lung fibrosis in mice and rats as quantified by UTE-MRI and histology. PLoS ONE. https://doi.org/10.1371/journal.pone.0063432
Erdmann VA, Barciszewska MZ, Szymanski M, Hochberg A, GrootBarciszewski NJ (2001) The non-coding RNAs as riboregulators. Nucleic Acids Res 29(1):189–193
Farkas-Himsley H, Hill R, Rosen B, Arab S, Lingwood C (1995) The bacterial colicin active against tumor cells in vitro and in vivo is verotoxin 1. Proc Natl Acad Sci 92(15):6996–7000
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
Gao Z, McClane BA (2012) Use of Clostridium perfringens enterotoxin and the enterotoxin receptor-binding domain (C-CPE) for cancer treatment: opportunities and challenges. J Toxicol. https://doi.org/10.1155/2012/981626
Gedde MM, Higgins DE, Tilney LG, Portnoy DA (2000) Role of listeriolysin O in cell-to-cell spread of Listeria monocytogenes. Infect Immun 68:999–1003
Goldufsky JWS, Hajihossainlou B, Rehman T, Majdobeh OL, Kaufman HE, Ruby CH, Shafikhani S (2015) Pseudomonas aeruginosa exotoxin T induces potent cytotoxicity against a variety of murine and human cancer cell lines. J Med Microbiol 64:164–173
Gontero P, Bohle A, Malmstrom P-U, O’Donnell MA, Oderda M, Sylvester R, Witjes F (2010) The role of bacillus Calmette-Guérin in the treatment of non–muscle-invasive bladder cancer. Eur Urol 57(3):410–429
Gunn GR, Zubair A, Peters C, Pan Z-K, Wu T-C, Paterson Y (2001) Two Listeria monocytogenes vaccine vectors that express different molecular forms of human papilloma virus-16 (HPV-16) E7 induce qualitatively different T cell immunity that correlates with their ability to induce regression of established tumors immortalized by HPV-16. J Immunol 167(11):6471–6479
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
Hong KH, Hong SK, Cho SI, Ra E, Han KH, Kang SB, Kim E-C, Park SS, Seong M-W (2016) Analysis of the vaginal microbiome by next-generation sequencing and evaluation of its performance as a clinical diagnostic tool in vaginitis. Ann Lab Med 36(5):441–449
Johnstone SA, Gelmon K, Mayer LD, Hancock RE, Bally MB (2000) In vitro characterization of the anticancer activity of membrane-active cationic peptides. I. Peptide-mediated cytotoxicity and peptide-enhanced cytotoxic activity of doxorubicin against wild-type and p-glycoprotein over-expressing tumor cell lines. Anticancer Drug Des 15(2):151–160
Jones A, Jonsson A-B, Aro H (2007) Neisseria gonorrhoeae infection causes a G1 arrest in human epithelial cells. FASEB J 21(2):345–355
Karpiński T, Szkaradkiewicz A, Gamian A (2013) New enterococcal anticancer peptide. In: Proceedings of the 23rd European Congress of Clinical Microbiology and Infectious Diseases. Berlin, Germany
Karpiński T (2012) New peptide (Entap) with anti-proliferative activity produced by bacteria of Enterococcus genus, Habilitation thesis. Scientific Publisher of Poznań University of Medical
Kaur B, Balgir PP, Mittu B, Kumar B, Garg N (2013) Biomedical applications of fermenticin HV6b isolated from Lactobacillus fermentum HV6b MTCC10770. BioMed Res Int. https://doi.org/10.1155/2013/168438
Lemichez E, Barbieri JT (2013) General aspects and recent advances on bacterial protein toxins. Cold Spring Harb Perspect Med 3(2):a013573
Leschner S, Westphal K, Dietrich N, Viegas N, Jablonska J, Lyszkiewicz M, Lienenklaus S, Falk W, Gekara N, Loessner H (2009) Tumor invasion of Salmonella enterica serovar Typhimurium is accompanied by strong hemorrhage promoted by TNF-α. PLoS ONE. https://doi.org/10.1371/journal.pone.0016369
Löfmark S, de Klerk N, Aro H (2011) Neisseria gonorrhoeae infection induces altered amphiregulin processing and release. PLoS ONE. https://doi.org/10.1371/journal.pone.0016369
Lorenzi PL, Reinhold WC, Rudelius M, Gunsior M, Shankavaram U, Bussey KJ, Scherf U, Eichler GS, Martin SE, Chin K (2006) Asparagine synthetase as a causal, predictive biomarker for L-asparaginase activity in ovarian cancer cells. Mol Cancer Ther 5(11):2613–2623
Lulla RR, Goldman S, Yamada T, Beattie CW, Bressler L, Pacini M, Pollack IF, Fisher PG, Packer RJ, Dunkel IJ (2016) Phase I trial of p28 (NSC745104), a non-HDM2-mediated peptide inhibitor of p53 ubiquitination in pediatric patients with recurrent or progressive central nervous system tumors: a pediatric brain tumor consortium study. Neuro Oncol 18(9):1319–1325
Macklaim JM, Cohen CR, Donders G, Gloor GB, Hill JE, Parham GP, Ravel J, Spear G, van de Wijgert J, Reid G (2012) Exploring a road map to counter misconceptions about the cervicovaginal microbiome and disease. Reprod Sci 19(11):1154–1162
Martarelli DP, Mazzoni MG (2009) Inhibition of adrenocortical carcinoma by diphtheria toxin mutant CRM197. Chemotherapy 55:425–432
Martin DH, Marrazzo JM (2016) The vaginal microbiome: current understanding and future directions. J infect Dis 214(1):S36–S41
Matsuo YK, Yamori T, Kasai H, Katsuta A, Adachi K, Shin-Ya K, Shizuri Y (2007) Urukthapelstatin A, a novel cytotoxic substance from marine-derived Mechercharimyces asporophorigenens YM11-542. I. Fermentation, isolation and biological activities. J Antibiot 60:251–25
McCarthy, E. F. (2006). "The toxins of William B. Coley and the treatment of bone and soft-tissue sarcomas." Iowa Orthopaedic J 26: 154.
Mehta RR, Yamada T, Taylor BN, Christov K, King ML, Majumdar D, Lekmine F, Tiruppathi C, Shilkaitis A, Bratescu L (2011) A cell penetrating peptide derived from azurin inhibits angiogenesis and tumor growth by inhibiting phosphorylation of VEGFR-2, FAK and Akt. Angiogenesis 14(3):355–369
Mizrahi A, Czerniak A, Levy T, Amiur S, Gallula J, Matouk I, Abu-lail R, Sorin V, Birman T, de Groot N (2009) Development of targeted therapy for ovarian cancer mediated by a plasmid expressing diphtheria toxin under the control of H19 regulatory sequences. J Transl Med 7(1):69
Mizrahi A, Czerniak A, Ohana P, Amiur S, Gallula J, Matouk I, Abu-lail R, Birman T, Hochberg A, Levy T (2010) Treatment of ovarian cancer ascites by intra-peritoneal injection of diphtheria toxin A chain-H19 vector: a case report. J Med Case Rep 4(1):228
Murphy J (2011) Mechanism of diphtheria toxin catalytic domain delivery to the eukaryotic cell cytosol and the cellular factors that directly participate in the process. Toxins 3:294–308
Obrig TG, Moran TP, Brown JE (1987) The mode of action of Shiga toxin on peptide elongation of eukaryotic protein synthesis. Biochem J 244:287–294
Oh H, Kim B-S, Seo S-S, Kong J-S, Lee J-K, Park S-Y, Hong K-M, Kim H-K, Kim M (2015) The association of uterine cervical microbiota with an increased risk for cervical intraepithelial neoplasia in Korea. Clin Microbiol Infect 21(7):674.e671-674.e679
Ohana P, Gofrit O, Ayesh S, Al-Sharef W, Mizrahi A, Birman T, Schneider T, Matouk I, de Groot N, Tavdy E (2004) Regulatory sequences of the H19 gene in DNA based therapy of bladder cancer. Gene Ther Mol Biol 8(8):181–192
Ohana P, Schachter P, Ayesh B, Mizrahi A, Birman T, Schneider T, Matouk I, Ayesh S, Kuppen PJ, de Groot N (2005) Regulatory sequences of H19 and IGF2 genes in DNA-based therapy of colorectal rat liver metastases. J Gene Med 7(3):366–374
Pec J Jr, Kliment J, Moravcik P, Fetisov I, Pecova K (1990) Isolation of Neisseria gonorrheae and concomitant bacterial microflora from urine obtained by suprapubic bladder puncture in women with gonococcal urethritis. Int Urol Nephrol 22(2):167–171
Piyathilake CJ, Ollberding NJ, Kumar R, Macaluso M, Alvarez RD, Morrow CD (2016) Cervical microbiota associated with higher grade cervical intraepithelial neoplasia in women infected with high-risk human papillomaviruses. Cancer Prev Res 9(5):357–366
Ravel J, Gajer P, Abdo Z, Schneider GM, Koenig SS, McCulle SL, Karlebach S, Gorle R, Russell J, Tacket CO (2011) Vaginal microbiome of reproductive-age women. Proc Natl Acad Sci 108(Supplement 1):4680–4687
Roberts NJ, Zhang L, Janku F, Collins A, Bai R-Y, Staedtke V, Rusk AW, Tung D, Miller M, Roix J (2014) Intratumoral injection of Clostridium novyi-NT spores induces antitumor responses. Sci Transl Med 6(249):249ra111
Sahl H-G, Bierbaum G (1998) Lantibiotics: biosynthesis and biological activities of uniquely modified peptides from gram-positive bacteria. Annu Rev Microbiol 52(1):41–79
Segerman ZJ, Roy B, Hecht SM (2013) Characterization of bleomycin-mediated cleavage of a hairpin DNA library. Biochemistry 52(31):5315–5327
Sidi AA, Ohana P, Benjamin S, Shalev M, Ransom JH, Lamm D, Hochberg A, Leibovitch I (2008) Phase I/II marker lesion study of intravesical BC-819 DNA plasmid in H19 over expressing superficial bladder cancer refractory to bacillus Calmette-Guerin. J Urol 180(6):2379–2383
Siegel RL, Miller KD, Jemal A (2019) Cancer statistics, 2019. CA Cancer J Clin 69(1):7–34
Taherian-Esfahani Z, Abedin-Do A, Nouri Z, Mirfakhraie R, Ghafouri-Fard S, Motevaseli E (2016) Lactobacilli differentially modulate mTOR and Wnt/β-catenin pathways in different cancer cell lines. Iran J Cancer Prev. https://doi.org/10.17795/ijcp-5369
Trabert B, Waterboer T, Idahl A, Brenner N, Brinton LA, Butt J, Coburn SB, Hartge P, Hufnagel K, Inturrisi F (2019) Antibodies against Chlamydia trachomatis and ovarian cancer risk in two independent populations. JNCI J Natl Cancer Inst 111(2):129–136
Van Belkum MJ, Martin-Visscher LA, Vederas JC (2011) Structure and genetics of circular bacteriocins. Trends Microbiol 19(8):411–418
Wood SJ, Goldufsky JW, Bello D, Masood S, Shafikhani SH (2015) Pseudomonas aeruginosa ExoT induces mitochondrial apoptosis in target host cells in a manner that depends on its GTPase-activating protein (GAP) domain activity. J Biol Chem 290(48):29063–29073
Wynn TA, Chawla A, Pollard JW (2013) Macrophage biology in development, homeostasis and disease. Nature 496(7446):445–455
Zhang Y, Zhang N, Zhao M, Hoffman RM (2015) Comparison of the selective targeting efficacy of Salmonella typhimurium A1-R and VNP20009 on the Lewis lung carcinoma in nude mice. Oncotarget 6(16):14625
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Yaghoubi, A., Khazaei, M., Ghazvini, K. et al. Bacterial Peptide and Bacteriocins in Treating Gynecological Cancers. Int J Pept Res Ther 28, 104 (2022). https://doi.org/10.1007/s10989-022-10411-3
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DOI: https://doi.org/10.1007/s10989-022-10411-3