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Protective Effect of Lactobacillus casei on DMH-Induced Colon Carcinogenesis in Mice

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Abstract

The administration of probiotics is a promising approach to reduce the prevalence of colon cancer, a multifactorial disease, with hereditary factors, as well as environmental lifestyle-related risk factors. Biogenic polyamines, putrescine, spermidine, and spermine are small cationic molecules with great roles in cell proliferation and differentiation as well as regulation of gene expression. Ornithine decarboxylase is the first rate-limiting enzyme for polyamine synthesis, and upregulation of ornithine decarboxylase activity and polyamine metabolism has been associated with abnormal cell proliferation. This paper is focused on studying the protective role of Lactobacillus casei ATCC 393 in a chemically induced mouse model of colon carcinogenesis, directing our attention on aberrant crypt foci as preneoplastic markers, and on polyamine metabolism as a possible key player in carcinogenesis. BALB/c mice were administered 1,2-dimethylhydrazine dihydrochloride (DMH) to induce colon cancer (20 mg/kg body weight, subcutaneous, twice a week for 24 weeks). L. casei ATCC 393 was given orally (106 CFU, twice a week), 2 weeks before DMH administration. Hematoxylin and eosin staining, high-performance liquid chromatography, and Western blotting were used to evaluate aberrant crypt foci, urinary polyamines, and ornithine decarboxylase expression in the colon. The experimental data showed that the preventive administration of L. casei ATCC 393 may delay the onset of cancer as it significantly reduced the number of DMH-induced aberrant crypt foci, the levels of putrescine, and the expression of ornithine decarboxylase. Hence, this probiotic strain has a prospective role in protection against colon carcinogenesis, and its antimutagenic activity may be associated with the maintenance of polyamine metabolism.

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References

  1. Azcárate-Peril MA, Sikes M, Bruno-Bárcena JM (2011) The intestinal microbiota, gastrointestinal environment and colorectal cancer: a putative role for probiotics in prevention of colorectal cancer? Am J Physiol Gastrointest Liver Physiol 301(3):G401–G424. doi:10.1152/ajpgi.00110.2011

    Article  Google Scholar 

  2. Pericleous M, Mandair D, Caplin ME (2013) Diet and supplements and their impact on colorectal cancer. J Gastrointest Oncol 4:409–423. doi:10.3978/j.issn.2078-6891.2013.003

    CAS  Google Scholar 

  3. Kumar KS, Sastry N, Polaki H, Mishra V (2015) Colon cancer prevention through probiotics: an overview. J Cancer Sci Ther 7(2):081–092. doi:10.4172/1948-5956.1000329

    CAS  Google Scholar 

  4. Mishra J, Drummond J, Quazi SH, Karanki SS, Shaw JJ, Chen B, Kumar N (2013) Prospective of colon cancer treatments and scope for combinatorial approach to enhanced cancer cell apoptosis. Crit Rev Oncol Hematol 86(3):232–250. doi:10.1016/j.critrevonc.2012.09.014

    Article  Google Scholar 

  5. Wargovich MJ, Brown VR, Morris J (2010) Aberrant crypt foci: the case for inclusion as a biomarker for colon cancer. Cancers 2(3):1705–1716. doi:10.3390/cancers2031705

    Article  CAS  Google Scholar 

  6. Kahouli I, Tomaro-Duchesneau C, Prakash S (2013) Probiotics in colorectal cancer (CRC) with emphasis on mechanisms of action and current perspectives. J Med Microbiol 62:1107–1123. doi:10.1099/jmm.0.048975-0

    Article  CAS  Google Scholar 

  7. Uccello M, Malaguarnera G, Basile F, D’agata V, Malaguarnera M, Bertino G, Vacante M, Drago F, Biondi A (2012) Potential role of probiotics on colorectal cancer prevention. BMC Surg 12(Suppl 1):S35. doi:10.1186/1471-2482-12-S1-S35

    Article  Google Scholar 

  8. Baffoni L, Gaggìa F, Di Gioia D, Biavati B (2012) Role of intestinal microbiota in colon cancer prevention. Ann Microbiol 62:15–30. doi:10.1007/s13213-011-0306-6

    Article  Google Scholar 

  9. Shmuely H, Domniz N, Cohen D (2013) Probiotics in the prevention of colorectal cancer. Curr Colorectal Cancer Rep 9(1):31–36. doi:10.1007/s11888-012-0153-2

    Article  Google Scholar 

  10. Patel S, Goyal A (2013) Evolving roles of probiotics in cancer prophylaxis and therapy. Probiotics Antimicro Prot 5(1):59–67. doi:10.1007/s12602-012-9124-9

    Article  Google Scholar 

  11. Serban DE (2014) Gastrointestinal cancers: influence of gut microbiota, probiotics and prebiotics. Cancer Lett 345(2):258–270. doi:10.1016/j.canlet.2013.08.013

    Article  CAS  Google Scholar 

  12. Chong ESL (2014) A potential role of probiotics in colorectal cancer prevention: review of possible mechanisms of action. World J Microbiol Biotechnol 30:351–374. doi:10.1007/s11274-013-1499-6

    Article  CAS  Google Scholar 

  13. Senan S, Prajapati JB, Joshi CG (2015) Feasibility of genome-wide screening for biosafety assessment of probiotics: a case study of Lactobacillus helveticus MTCC 5463. Probiotics Antimicro Prot 7(4):249–258. doi:10.1007/s12602-015-9199-1

    Article  CAS  Google Scholar 

  14. Di Cerbo A, Palmieri B, Aponte M, Morales-Medina JC, Iannitti T (2016) Mechanisms and therapeutic effectiveness of lactobacilli. J Clin Pathol 69(3):187–203. doi:10.1136/jclinpath-2015-202976

    Article  CAS  Google Scholar 

  15. Chandra P (2016) Effect of lactobacillus on biological properties: anticancer, immunomodulatory properties and improvement of bone health. J Microbiol Biotech Res 6(3):17–23

    Article  Google Scholar 

  16. Ishikawa H, Akedo I, Otani T, Suzuki T, Nakamura T, Takeyama I, Ishiguro S, Miyaoka E, Sobue T, Kakizoe T (2005) Randomized trial of dietary fiber and Lactobacillus casei administration for prevention of colorectal tumors. Int J Cancer 116(5):762–767. doi:10.1002/ijc.21115

    Article  CAS  Google Scholar 

  17. Choi SS, Kim Y, Han KS, You S, Oh S, Kim SH (2006) Effects of lactobacillus strains on cancer cell proliferation and oxidative stress in vitro. Lett Appl Microbiol 42(5):452–458. doi:10.1111/j.1472-765X.2006.01913.x

    Article  CAS  Google Scholar 

  18. Tiptiri-Kourpeti A, Spyridopoulou K, Santarmaki V, Aindelis G, Tompoulidou E, Lamprianidou EE, Saxami G, Ypsilantis P, Lampri ES, Simopoulos C, Kotsianidis I, Galanis A, Kourkoutas Y, Dimitrellou D, Chlichlia K (2016) Lactobacillus casei exerts anti-proliferative effects accompanied by apoptotic cell death and up-regulation of TRAIL in colon carcinoma cells. PLoS One 11(2):e0147960. doi:10.1371/journal.pone.0147960

    Article  Google Scholar 

  19. Saxami G, Ypsilantis P, Sidira M, Simopoulos C, Kourkoutas Y, Galanis A (2012) Distinct adhesion of probiotic strain Lactobacillus casei ATCC 393 to rat intestinal mucosa. Anaerobe 18(4):417–420. doi:10.1016/j.anaerobe.2012.04.002

    Article  CAS  Google Scholar 

  20. Mandal S, Mandal A, Johansson HE, Orjalo AV, Park MH (2013) Depletion of cellular polyamines, spermidine and spermine, causes a total arrest in translation and growth in mammalian cells. Proc Natl Acad Sci U S A 110(6):2169–2174. doi:10.1073/pnas.1219002110

    Article  CAS  Google Scholar 

  21. Nowotarski SL, Woster PM, Casero RA Jr (2013) Polyamines and cancer: implications for chemotherapy and chemoprevention. Expert Rev Mol Med 15:e3. doi:10.1017/erm

    Article  Google Scholar 

  22. Pegg AE (2016) Functions of polyamines in mammals. J Biol Chem 291(29):14904–14912. doi:10.1074/jbc.R116.731661

    Article  CAS  Google Scholar 

  23. Russo F, Linsalata M, Orlando A (2014) Probiotics against neoplastic transformation of gastric mucosa: effects on cell proliferation and polyamine metabolism. World J Gastroenterol 20(37):13258–13272. doi:10.3748/wjg.v20.i37.13258

    Article  Google Scholar 

  24. Kusano T, Suzuki H (2015) Polyamines: a universal molecular nexus for growth, survival, and specialized metabolism. Springer, Tokyo

    Book  Google Scholar 

  25. Paik MJ, Kuon D, Cho J, Kim KR (2009) Altered urinary polyamine patterns in cancer patients under acupuncture therapy. Amino Acids 37:407–413. doi:10.1007/s00726-008-0169-8

    Article  CAS  Google Scholar 

  26. Nakayama Y, Torigoe T, Minagawa N, Yamaguchi K (2012) The clinical usefulness of urinary N1,N12-diacetylspermine (DiAcSpm) levels as a tumor marker in patients with colorectal cancer. Oncol Lett 2:970–974. doi:10.3892/ol.2012.625

    Google Scholar 

  27. Babbar N, Gerner EW (2011) Targeting polyamines and inflammation for cancer prevention. Recent Results Cancer Res 188:49–64. doi:10.1007/978-3-642-10858-7_4

    Article  CAS  Google Scholar 

  28. Chen CC, Lin WC, Kong MS, Shi HN, Walker WA, Lin CY, Huang CT, Lin YC, Jung SM, Lin TY (2012) Oral inoculation of probiotics Lactobacillus acidophilus NCFM suppresses tumour growth both in segmental orthotopic colon cancer and extra-intestinal tissue. Br J Nutr 107:1623–1634. doi:10.1017/S0007114511004934

    Article  CAS  Google Scholar 

  29. Zamora-González EO, Santerre A, Palomera-Avalos V, Morales-Villagrán A (2013) A chronic combinatory stress model that activates the HPA axis and avoids habituation in BALB/c mice. J Neurosci Meth 213:70–75. doi:10.1016/j.jneumeth.2012.10.015

    Article  Google Scholar 

  30. NOM-062-ZOO-1999 (1999) Norma oficial mexicana, especificaciones técnicas para la producción, cuidado y uso de los animales de Laboratorio. http://www.fmvz.unam.mx/fmvz/principal/archivos/062ZOO.PDF. Accessed 31 October 2013

  31. Rosenberg DW, Giardina C, Tanaka T (2009) Mouse models for the study of colon carcinogenesis. Carcinogenesis 30:183–196. doi:10.1093/carcin/bgn267

    Article  CAS  Google Scholar 

  32. Hahn ED, Soyer R (2005) Probit and logit models: Differences in a Multivariate Realm. http://home.gwu.edu/_soyer/mv1h.pdf, accessed 20 July 2016

  33. Kiernan JA (2008) Histological and histochemical methods: theory and practice. Scion Publishing, UK

    Google Scholar 

  34. Farkas S, Hajós G (1998) Monitoring of biologically active amines in cereals and cereal based food products by HPLC. Chromatographia 48:37–42. doi:10.1007/BF02467513

    Article  CAS  Google Scholar 

  35. Chi W, Song X, Jiang C, Liu X, Li W, Wang X (2006) Lentiviral vector-mediated downregulation of ornithine decarboxylase inhibits tumor cell growth in vitro and in vivo. Tumor Biol 27:243–251. doi:10.1159/000094843

    Article  CAS  Google Scholar 

  36. Kim SN, Lee WM, Park KS, Kim JB, Han DJ, Bae J (2015) The effect of Lactobacillus casei extract on cervical cancer cell lines. Contemp Oncol (Pozn) 19(4):306–312. doi:10.5114/wo.2014.45292

    Google Scholar 

  37. Soltan Dallal MM, Mojarrad M, Salehipour Z, Atapour Mashhad H, Raoofian R, Rajabi Z (2012) Effects of probiotic lactobacillus acidophilus and lactobacillus casei on the behavior of colorectal tumor cells. Tehran Univ Med J 70(4):220–227

    Google Scholar 

  38. Lenoir M, Del Carmen S, Cortes-Perez NG, Lozano-Ojalvo D, Muñoz-Provencio D, Chain F, Langella P, de Moreno de LeBlanc A, LeBlanc JG, Bermúdez-Humarán LG (2016) Lactobacillus casei BL23 regulates Treg and Th17 T-cell populations and reduces DMH-associated colorectal cancer. J Gastroenterol doi. doi:10.1007/s00535-015-1158-9

    Google Scholar 

  39. Corpet DE, Taché S (2002) Most effective colon cancer chemopreventive agents in rats: a systematic review of aberrant crypt foci and tumor data, ranked by potency. Nutr Cancer 43(1):1–21. doi:10.1207/S15327914NC431_1

    Article  CAS  Google Scholar 

  40. Park E, Jeon GI, Park JS, Paik HD (2007) A probiotic strain of Bacillus polyfermenticus reduces DMH induced precancerous lesions in F344 male rat. Biol Pharm Bull 30(3):569–574

    Article  CAS  Google Scholar 

  41. Verma A, Shukla G (2013) Probiotics Lactobacillus rhamnosus GG, Lactobacillus acidophilus suppresses DMH-induced procarcinogenic fecal enzymes and preneoplastic aberrant crypt foci in early colon carcinogenesis in Sprague Dawley rats. Nutr Cancer 65(1):84–91. doi:10.1080/01635581.2013.741746

    Article  Google Scholar 

  42. Ohland CL, Macnaughton WK (2010) Probiotic bacteria and intestinal epithelial barrier function. Am J Physiol Gastrointest Liver Physiol 298(6):G807–G819. doi:10.1152/ajpgi.00243.2009

    Article  CAS  Google Scholar 

  43. Le Leu RK, Brown IL, Hu Y, Bird AR, Jackson M, Esterman A, Young GP (2005) A synbiotic combination of resistant starch and Bifidobacterium lactis facilitates apoptotic deletion of carcinogen-damaged cells in rat colon. J Nutr 135(5):996–1001

    CAS  Google Scholar 

  44. Raman M, Ambalam P, Kondepudi KK, Pithva S, Kothari C, Patel AT, Purama RK, Dave JM, Vyas BR (2013) Potential of probiotics, prebiotics and synbiotics for management of colorectal cancer. Gut Microbes 4(3):181–192. doi:10.4161/gmic.23919

    Article  Google Scholar 

  45. Kumar M, Nagpal R, Verma V, Kumar A, Kaur N, Hemalatha R, Gautam SK, Singh B (2013) Probiotic metabolites as epigenetic targets in the prevention of colon cancer. Nutr Rev 71(1):23–34. doi:10.1111/j.1753-4887.2012.00542.x

    Article  Google Scholar 

  46. McIntyre RE, Buczacki SJA, Arends MJ, Adams DJ (2015) Mouse models of colorectal cancer as preclinical models. BioEssays 37(8):909–920. doi:10.1002/bies.201500032

    Article  Google Scholar 

  47. Gerner EW, Meyskens FL Jr (2004) Polyamines and cancer: old molecules, new understanding. Nat Rev Cancer 4(10):781–792

    Article  CAS  Google Scholar 

  48. Babbar N, Gerner EW (2011) Targeting polyamines and inflammation for cancer prevention. Recent Res Cancer 188:49–64. doi:10.1007/978-3-642-10858-7_4

    Article  CAS  Google Scholar 

  49. Soda K (2011) The mechanisms by which polyamines accelerate tumor spread. J Exp Clin Cancer Res 30:95. doi:10.1186/1756-9966-30-95

    Article  CAS  Google Scholar 

  50. Ramani D, De Bandt JP, Cynober L (2014) Aliphatic polyamines in physiology and diseases. Clin Nutr 33:14–22. doi:10.1016/j.clnu.2013.09.019

    Article  CAS  Google Scholar 

  51. Reddy BS (1999) Possible mechanisms by which pro- and prebiotics influence colon carcinogenesis and tumor growth. J Nutr 129(7 Suppl):1478S–1482S

    CAS  Google Scholar 

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Acknowledgements

This study was supported by the Consejo Nacional de Ciencia y Tecnología (CONACyT, grant # salud-2008-C01 87231) and Consejo Estatal de Ciencia y Tecnología de Jalisco (COECyTJAL, grant # 25-2008-617). The first author received a Ph.D. grant from the Consejo Nacional de Ciencia y Tecnología (CONACyT) México.

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  1. Departamento de Salud, El Colegio de La Frontera Sur, Periférico Sur s/n, María Auxiliadora, 29290, San Cristóbal de Las Casas, Chiapas, Mexico

    Cesar Antonio Irecta-Nájera

  2. Departamento de Biología Celular y Molecular, Centro Universitario de Ciencias Biológicas y Agropecuarias, Carretera Guadalajara-Nogales Km 15.5, Las Agujas, C.P. 45110, Zapopan, Jalisco, Mexico

    María del Rosario Huizar-López, Josefina Casas-Solís, Patricia Castro-Félix & Anne Santerre

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  1. Cesar Antonio Irecta-Nájera
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Correspondence to Anne Santerre.

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Irecta-Nájera, C.A., del Rosario Huizar-López, M., Casas-Solís, J. et al. Protective Effect of Lactobacillus casei on DMH-Induced Colon Carcinogenesis in Mice. Probiotics & Antimicro. Prot. 9, 163–171 (2017). https://doi.org/10.1007/s12602-017-9253-2

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