The Effect of Acute and Chronic Infection-Induced by AvrA Protein of Salmonella typhimurium on Radical Oxygen Species, Phosphatase and Tensin Homolog, and Cellular Homolog Expression During the Development of Colon Cancer

Satuman Satuman; Desi Sandra Sari; Eva Rachmi; Eddy Herman Tanggo; Hari Basuki Notobroto; Ketut Sudiana; Sofia Mubarika; Fedik Abdul Rantam; Soemarno Soemarno; Eddy Bagus Warsito

doi:10.3889/oamjms.2021.4945

Authors

Satuman Satuman Doctoral Student of Medical Science, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia; Laboratory of Human Physiology, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia
Desi Sandra Sari Department of Periodontal, Faculty of Dentistry, Universitas Jember, Jember Regency, Indonesia
Eva Rachmi Laboratory of Anatomy, Faculty of Medicine, Universitas Mulawarman, Samarinda, Indonesia
Eddy Herman Tanggo Departement of Oncology, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
Hari Basuki Notobroto Department of Biostatistics and Population Studies Statistic, Faculty of Public Health, Universitas Airlangga, Surabaya, Indonesia
Ketut Sudiana Department of Pathology Anatomy, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
Sofia Mubarika Department of Anatomy and Histology, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia
Fedik Abdul Rantam Stem Cells Research and Development Center, Universitas Airlangga, Surabaya, Indonesia; Department of Virology, Microbiology, and Immunology, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, Indonesia
Soemarno Soemarno Department of Microbiology, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia
Eddy Bagus Warsito Department of Microbiology, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia

DOI:

https://doi.org/10.3889/oamjms.2021.4945

Keywords:

AvrA, Salmonella, Colorectal cancer, Radical oxygen species, Phosphatase and tensin homolog, Cellular homolog

Abstract

AIM. The aim of the study was to analyze Avra's effector in inducing cancer stem cells into colon cancer through increased radical oxygen species (ROS), PTEN expression and c-myC as markers of tumorigenesis in mice model of the colorectal cancer infected with S. typhimurium.

METHODS. The study used balb c mice induced once a week by 10 mg / mL / day of AOM for 1-week and 12-week treatment period. Isolation of S. typhimurium specific protein had been carried out before being induced to mice in intraperitoneal manner in the amount of 40 mL / 50 mL. Propagation of S. typhimurium ATCC bacteria with MacConkey media and isolation of S. typhimurium protein were administered. The sample was divided into 4 groups, positive control group (group that was only exposed to azoxymethane (AOM), group exposed to both AOM and AvrA (AOM + AvrA), and group exposed to both AOM and S. typhimurium (AOM + S. typhimurium). Blood flow cytometry and soft tissue sampling for IHC and data analysis were then conducted.

RESULTS. The results of the study showed that there was an increase in the expression of ROS, PTEN and c-Myc. Increased ROS expression was found in the 12-week treatment period group and it was known that such increase was due to AOM + S. typhimurium (45.78 Â± 2.93) induction compared to AOM, AOM + AvrA and control (p <0.05). PTEN and C-myc expression increased at the 12th week compared to the negative control.

CONCLUSION. Inflammation is the triggering factor for colorectal cancer, in which the expression of ROS, PTEN and c-Myc as the colorectal cancer markers increases in both the acute and chronic phases.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

References

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424. https://doi.org/10.3322/caac.21492 PMid:30207593 DOI: https://doi.org/10.3322/caac.21492

Sun J, Kato I. Gut microbiota, inflammation and colorectal cancer. Genes Dis. 2016;3(2):130-43. PMid:28078319 DOI: https://doi.org/10.1016/j.gendis.2016.03.004

Gunn JS, Marshall JM, Baker S, Dongol S, Charles RC, Ryan ET. Salmonella chronic carriage: Epidemiology, diagnosis, and gallbladder persistence. Trends Microbiol. 2014;22(11):648-55. https://doi.org/10.1016/j.tim.2014.06.007 PMid:25065707 DOI: https://doi.org/10.1016/j.tim.2014.06.007

Lu R, Bosland M, Xia Y, Zhang YG, Kato I, Sun J. Presence of Salmonella AvrA in colorectal tumor and its precursor lesions in mouse intestine and human specimens. Oncotarget. 2017;8(33):55104-15. https://doi.org/10.18632/oncotarget.19052 PMid:28903406 DOI: https://doi.org/10.18632/oncotarget.19052

Mittrücker HW, Kaufmann SH. Immune response to infection with Salmonella typhimurium in mice. J Leukoc Biol. 2000;67(4):457-63. https://doi.org/10.1002/jlb.67.4.457 PMid:10770276 DOI: https://doi.org/10.1002/jlb.67.4.457

Munro MJ, Wickremesekera SK, Peng L, Tan ST, Itinteang T. Cancer stem cells in colorectal cancer: A review. J Clin Pathol. 2018;71(2):110-6. https://doi.org/10.1136/jclinpath-2017-204739 PMid:28942428 DOI: https://doi.org/10.1136/jclinpath-2017-204739

Crump JA, Mintz ED. Global trends in typhoid and paratyphoid fever. Clin Infect Dis. 2010;50(2):241-6. https://doi.org/10.1086/649541 PMid:20014951 DOI: https://doi.org/10.1086/649541

Pastille E, Bardini K, Fleissner D, Adamczyk A, Frede A, Wadwa M, et al. Transient ablation of regulatory T cells improves antitumor immunity in colitis-associated colon cancer. Cancer Res. 2014;74(16):4258-69. https://doi.org/10.1158/0008-5472.can-13-3065 PMid:24906621 DOI: https://doi.org/10.1158/0008-5472.CAN-13-3065

Wu D, Yotnda P. Production and detection of reactive oxygen species (ROS) in cancers. J Vis Exp. 2011;57:3357. PMid:22127014 DOI: https://doi.org/10.3791/3357

Durban VM, Jansen M, Davies EJ, Morsink FH, Offerhaus GJ, Clarke AR. Epithelial-specific loss of PTEN results in colorectal juvenile polyp formation and invasive cancer. Am J Pathol. 2014;184(1):86-91. https://doi.org/10.1016/j.ajpath.2013.10.003 PMid:24200851 DOI: https://doi.org/10.1016/j.ajpath.2013.10.003

Iwata T, Schultz D, Hicks J, Hubbard GK, Mutton LN, Lotan TL, et al. MYC overexpression induces prostatic intraepithelial neoplasia and loss of Nkx3.1 in mouse luminal epithelial cells. PLoS One. 2010;5(2):e9427. https://doi.org/10.1371/journal.pone.0009427 PMid:20195545 DOI: https://doi.org/10.1371/journal.pone.0009427

Mughini-Gras L, Schaapveld M, Kramers J, Mooij S, Neefjes- Borst EA, Pelt WV, et al. Increased colon cancer risk after severe Salmonella infection. PLoS One. 2018;13(1):e0189721. https://doi.org/10.1371/journal.pone.0189721 PMid:29342165 DOI: https://doi.org/10.1371/journal.pone.0189721

Zha L, Garrett S, Sun J. Salmonella infection in chronic inflammation and gastrointestinal cancer. Diseases. 2019;7(1):28. https://doi.org/10.3390/diseases7010028 PMid:30857369 DOI: https://doi.org/10.3390/diseases7010028

Haghjoo E, Galán JE. Salmonella typhi encodes a functional cytolethal distending toxin that is delivered into host cells by a bacterial-internalization pathway. Proc Natl Acad Sci USA. 2004;101(13):4614-9. https://doi.org/10.1073/pnas.0400932101 PMid:15070766 DOI: https://doi.org/10.1073/pnas.0400932101

Liu X, Lu R, Xia Y, Wu S, Sun J. Eukaryotic signaling pathways targeted by Salmonella effector protein AvrA in intestinal infection in vivo. BMC Microbiol. 2010;10:326. https://doi.org/10.1186/1471-2180-10-326 PMid:21182782 DOI: https://doi.org/10.1186/1471-2180-10-326

Chen J, Huang XF. The signal pathways in azoxymethane-induced colon cancer and preventive implications. Cancer Biol Ther. 2009;8(14):1313-7. https://doi.org/10.4161/cbt.8.14.8983 PMid:19502780 DOI: https://doi.org/10.4161/cbt.8.14.8983

Yaduvanshi SK, Srivastava N, Marotta F, Jain S, Yadav H. Evaluation of micronuclei induction capacity and mutagenicity of organochlorine and organophosphate pesticides. Drug Metab Lett. 2012;6(3):187-97. https://doi.org/0.2174/1872312811206030006 PMid:23092307 DOI: https://doi.org/10.2174/1872312811206030006

Gekara NO. DNA damage-induced immune response: Micronuclei provide key platform. J Cell Biol. 2017;216(10):2999- 3001. https://doi.org/10.1083/jcb.201708069 PMid:28860276 DOI: https://doi.org/10.1083/jcb.201708069

Tan HY, Wang N, Li S, Hong M, Wang X, Feng Y. The reactive oxygen species in macrophage polarization: Reflecting its dual role in progression and treatment of human diseases. Oxid Med Cell Longev. 2016;2016:2795090. https://doi.org/10.1155/2016/2795090 PMid:27143992 DOI: https://doi.org/10.1155/2016/2795090

Lee SH, Almutairi S, Ali AK. Reactive oxygen species modulate immune cell effector function. J Immunol. 2017;198(1):222.20.

Yarosz EL, Chang CH. The role of reactive oxygen species in regulating T cell-mediated immunity and disease. Immune Netw. 2018;18(1):e14. https://doi.org/10.4110/in.2018.18.e14 PMid:29503744 DOI: https://doi.org/10.4110/in.2018.18.e14

Feng YY, Tang M, Suzuki M, Gunasekara C, Anbe Y, Hiraoka Y, et al. Essential role of NADPH oxidase-dependent production of reactive oxygen species in maintenance of sustained B cell receptor signaling and B cell proliferation. J Immunol. 2019;202(9):2546-57. https://doi.org/10.4049/jimmunol.1800443 PMid:30867238 DOI: https://doi.org/10.4049/jimmunol.1800443

Virág L, Jaén RI, Regdon Z, Boscá L, Prieto P. Self-defense of macrophages against oxidative injury: Fighting for their own survival. Redox Biol. 2019;26:101261. https://doi.org/10.1016/j.redox.2019.101261 PMid:31279985 DOI: https://doi.org/10.1016/j.redox.2019.101261

Grisham MB, Jourd’heuil D, Wink DA. Review article: Chronic inflammation and reactive oxygen and nitrogen metabolism-implications in DNA damage and mutagenesis. Aliment Pharmacol Ther. 2000;14 Suppl 1:3-9. https://doi.org/10.1046/j.1365-2036.2000.014s1003.x PMid:10807397 DOI: https://doi.org/10.1046/j.1365-2036.2000.014s1003.x

Lu R, Wu S, Zhang YG, Xia Y, Zhou Z, Kato I, et al. Salmonella protein AvrA activates the STAT3 signaling pathway in colon cancer. Neoplasia. 2016;18(5):307-16. https://doi.org/10.1016/j.neo.2016.04.001 PMid:27237322 DOI: https://doi.org/10.1016/j.neo.2016.04.001

Zeineldin M, Neufeld KI. New insights from animal models of colon cancer: Inflammation control as a new facet on the tumor suppressor APC gem. Gastrointest Cancer. 2015:5:39-52. https://doi.org/10.2147/gictt.s51386 DOI: https://doi.org/10.2147/GICTT.S51386

Zhan T, Ambrosi G, Wandmacher AM, Rauscher B, Betge J, Rindtorff N, et al. MEK inhibitors activate Wnt signalling and induce stem cell plasticity in colorectal cancer. Nat Commun. 2019;10(1):2197. https://doi.org/10.1038/s41467-019-09898-0 PMid:31097693 DOI: https://doi.org/10.1038/s41467-019-09898-0

Sun Y, Tian H, Wang L. Effects of PTEN on the proliferation and apoptosis of colorectal cancer cells via the phosphoinositol-3-kinase/Akt pathway. Oncol Rep. 2015;33(4):1828-36. https://doi.org/10.3892/or.2015.3804 PMid:25683168 DOI: https://doi.org/10.3892/or.2015.3804

Chen CY, Chen J, He L, Stiles BL. PTEN: Tumor suppressor and metabolic regulator. Front Endocrinol (Lausanne). 2018;9:338. https://doi.org/10.3389/fendo.2018.00338 PMid:30038596 DOI: https://doi.org/10.3389/fendo.2018.00338

Ming M, He YY. PTEN in DNA damage repair. Cancer Lett. 2012;319(2):125-9. PMid:22266095 DOI: https://doi.org/10.1016/j.canlet.2012.01.003

Salvatore L, Calegari MA, Loupakis F, Fassan M, Di Stefano B, Bensi M, et al. PTEN in colorectal cancer: Shedding light on its role as predictor and target. Cancers (Basel). 2019;11(11):1765. https://doi.org/10.3390/cancers11111765 PMid:31717544 DOI: https://doi.org/10.3390/cancers11111765

Kotelevets L, Scott MGH, Chastre E. Targeting PTEN in colorectal cancers. Adv Exp Med Biol. 2018;1110:55-73. PMid:30623366 DOI: https://doi.org/10.1007/978-3-030-02771-1_5

Stecher B, Robbiani R, Walker AW, Westendorf AM, Barthel M, Kremer M, et al. Salmonella enterica serovar typhimurium exploits inflammation to compete with the intestinal microbiota. PLoS Biol. 2007;5(10):2177-89. https://doi.org/10.1371/journal.pbio.0050244 PMid:17760501 DOI: https://doi.org/10.1371/journal.pbio.0050244

Miller R, Wiedmann M. Dynamic duo-the Salmonella cytolethal distending toxin combines ADP-ribosyltransferase and nuclease activities in a novel form of the cytolethal distending toxin. Toxins (Basel). 2016;8(5):121. https://doi.org/10.3390/toxins8050121 PMid:27120620 DOI: https://doi.org/10.3390/toxins8050121

Hernández-Luna M, PMuñóz-López P, Aguilar-González CA, Luria-Pérez R. Infection by Salmonella enterica promotes or demotes tumor development. In: Salmonella-A Re-Emerging Pathogen. London: Intech Open; 2018. https://doi.org/10.5772/intechopen.75481 DOI: https://doi.org/10.5772/intechopen.75481

Persad A, Venkateswaran G, Hao L, Garcia ME, Yoon J, Sidhu J, et al. Active β-catenin is regulated by the PTEN/PI3 kinase pathway: A role for protein phosphatase PP2A. Genes Cancer. 2016;7(11-12):368-82. https://doi.org/10.18632/genesandcancer.128 PMid:28191283 DOI: https://doi.org/10.18632/genesandcancer.128

Liu X, Lu R, Wu S, Sun J. Salmonella regulation of intestinal stem cells through the Wnt/beta-catenin pathway. FEBS Lett. 2010;584(5):911-6. https://doi.org/10.1016/j.febslet.2010.01.024 PMid:20083111 DOI: https://doi.org/10.1016/j.febslet.2010.01.024

Dang CV, O’Donnell KA, Zeller KI, Nguyen T, Osthus RC, Li F. The c-Myc target gene network. Semin Cancer Biol. 2006;16(4):253-64. https://doi.org/10.1016/j.semcancer.2006.07.014 PMid:16904903 DOI: https://doi.org/10.1016/j.semcancer.2006.07.014

Lee KS, Kwak Y, Nam KH, Kim DW, Kang SB, Choe G, et al. c-MYC copy-number gain is an independent prognostic factor in patients with colorectal cancer. PLoS One. 2015;10(10):e0139727. https://doi.org/10.1371/journal.pone.0139727 PMid:26426996 DOI: https://doi.org/10.1371/journal.pone.0139727

Elbadawy M, Usui T, Yamawaki H, Sasaki K. Emerging roles of C-Myc in cancer stem cell-related signaling and resistance to cancer chemotherapy: A potential therapeutic target against colorectal cancer. Int J Mol Sci. 2019;20(9):2340. https://doi.org/10.3390/ijms20092340 PMid:31083525 DOI: https://doi.org/10.3390/ijms20092340

Lu R, Wu S, Zhang YG, Xia Y, Liu X, Zheng Y, et al. Enteric bacterial protein AvrA promotes colonic tumorigenesis and activates colonic beta-catenin signaling pathway. Oncogenesis. 2014;3(6):e105. https://doi.org/10.1038/oncsis.2014.20 PMid:24911876 DOI: https://doi.org/10.1038/oncsis.2014.20

Moumen M, Chiche A, Decraene C, Petit V, Gandarillas A, Deugnier MA, et al. Myc is required for β-catenin-mediated mammary stem cell amplification and tumorigenesis. Mol Cancer. 2013;12(1):132. https://doi.org/10.1186/1476-4598-12-132 PMid:24171719 DOI: https://doi.org/10.1186/1476-4598-12-132

Hunt CR, Sim JE, Sullivan SJ, Featherstone T, Golden W, Von Kapp-Herr C, et al. Genomic instability and catalase gene amplification induced by chronic exposure to oxidative stress. Cancer Res. 1998;58(17):3986-92. PMid:9731512

Tan SN, Sim SP, Khoo AS. Oxidative stress-induced chromosome breaks within the ABL gene: A model for chromosome rearrangement in nasopharyngeal carcinoma. Hum Genomics 2018;12(1):29. https://doi.org/10.1186/s40246-018-0160-8 PMid:29914565 DOI: https://doi.org/10.1186/s40246-018-0160-8

Liu H, Lu W, He H, Wu J, Zhang C, Gong H, et al. Inflammation-dependent overexpression of c-Myc enhances CRL4DCAF4 E3 ligase activity and promotes ubiquitination of ST7 in colitis-associated cancer. J Pathol. 2019;248(4):464-75. https://doi.org/10.1002/path.5273 PMid:30945288 DOI: https://doi.org/10.1002/path.5273

Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454(7203):436-44. https://doi.org/10.1038/nature07205 PMid:18650914 DOI: https://doi.org/10.1038/nature07205

Zhang HL, Wang P, Lu MZ, Zhang SD, Zheng L. c-Myc maintains the self-renewal and chemoresistance properties of colon cancer stem cells. Oncol Lett. 2019;17(5):4487-93. https://doi.org/10.3892/ol.2019.10081 PMid:30944638 DOI: https://doi.org/10.3892/ol.2019.10081