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Introduction: Breast cancer is one of the important causes of mortality among women. Many studies have focused on the development of natural health products for prevention and treatment of breast cancer. This study investigated the effects of B. bifidum and its microvesicles (MVs) on 4T1-induced breast cancer in BALB/c mice. Methods: 60 female BALB/c mice were divided into 5 groups: (1) negative control, (2) positive control, (3) doxorubicin, (4) probiotic and (5) MVs (isolated from B. bifidum culture by centrifugation at 70000×g). The mice in groups 4 and 5 were pretreated with B. bifidum and MVs for 4 weeks, respectively. Tumor was induced by subcutaneous administration of 4T1 cell culture. After tumor development, mice in group 3 were treated with doxorubicin while other groups were treated as before. The mice were sacrificed after 3 weeks, breast tumors were removed and histologically examined. Also, P53 and Ki67 protein were evaluated by IHC staining, and P53 gene expression was assessed by RT-PCR. Results: Pretreatment with MVs and probiotic reduced mortality and tumor growth rate. MVs and Probiotic prevented the weight loss and suppressed tumor cell proliferation which was indicated by Ki-67 and p53. The expression of p53 confirmed these results. Despite the malignancy in the breast tissue, necrosis of cancer cells occurred in the mice treated with MVs. Conclusion: MVs of B. bifidum effectively inhibited breast cancer development in mice and suppressed tumor cell proliferation. Probiotic microorganisms and their metabolites can be used as a functional food to prevent breast cancer.
Types of Manuscript: Experimental research article | Subject: Others

1. Aad G, Abbott B, Abdallah J, Abdelalim A, Abdesselam A, Abdinov O, et al. Electron performance measurements with the ATLAS detector using the 2010 LHC proton-proton collision data. Eur Phys J C 2012; 72: 1909. [DOI:10.1140/epjc/s10052-012-1909-1]
2. Aragon F, Carino S, Perdigon G, de Moreno de LeBlanc A. Inhibition of growth and metastasis of breast cancer in mice by milk fermented with Lactobacillus casei CRL 431. J Immunother 2015; 38: 185-196. [DOI:10.1097/CJI.0000000000000079]
3. Baliga MS, Meleth S, Katiyar SK. Growth inhibitory and antimetastatic effect of green tea polyphenols on metastasis-specific mouse mammary carcinoma 4T1 cells in vitro and in vivo systems. Clin Cancer Res 2005; 11: 1918-1927. [DOI:10.1158/1078-0432.CCR-04-1976]
4. Bao L, Haque A, Jackson K, Hazari S, Moroz K, Jetly R, et al. Increased expression of Pglycoprotein is associated with doxorubicin chemoresistance in the metastatic 4T1 breast cancer model. Am J Pathol 2011; 178: 838-852. [DOI:10.1016/j.ajpath.2010.10.029]
5. Cardiff RD, Miller CH, Munn RJ. Manual hematoxylin and eosin staining of mouse tissue sectionsCold Spring Harb. Protoc 2014; 2014: 655-658. [DOI:10.1101/pdb.prot073411]
6. Doroshow J, Locker G Y, Ifrim I, Myers C E. Prevention of doxorubicin cardiac toxicity in the mouse by N-acetylcysteine. J Clin Investig 1981; 68: 1053-1064. [DOI:10.1172/JCI110328]
7. DuPre SA, Redelman D, Hunter JrKW. The mouse mammary carcinoma 4T1: characterization of the cellular landscape of primary tumours and metastatic tumour foci. Int J Exp Pathol 2007; 88: 351-360. [DOI:10.1111/j.1365-2613.2007.00539.x]
8. Fearon K, Arends J, Baracos V. Understanding the mechanisms and treatment options in cancer cachexia. Nat Rev Clin Oncol 2013; 10: 90-99. [DOI:10.1038/nrclinonc.2012.209]
9. Ganguly N, Bhattacharya S, Sesikeran B, Nair G, Ramakrishna B, Sachdev H, et al. ICMR-DBT guidelines for evaluation of probiotics in food. Indian J Med Res 2011; 134: 22-25.
10. Jadidi-Niaragh F, Atyabi F, Rastegari A, Kheshtchin N, Arab S, Hassannia H, et al. CD73 specific siRNA loaded chitosan lactate nanoparticles potentiate the antitumor effect of a dendritic cell vaccine in 4T1 breast cancer bearing mice. J Control Release 2017; 246: 46-59. [DOI:10.1016/j.jconrel.2016.12.012]
11. John EM, Hines LM, Phipps AI, Koo J, Longacre TA, Ingles SA, et al. Reproductive history, breast‐feeding and risk of triple negative breast cancer: The Breast Cancer Etiology in Minorities (BEM) study. Int J Cancer 2018; 142: 2273-2285. [DOI:10.1002/ijc.31258]
12. Kaparakis M, Turnbull L, Carneiro L, Firth S, Coleman HA, Parkington HC, et al. Bacterial membrane vesicles deliver peptidoglycan to NOD1 in epithelial cells. Cell Microbiol 2010; 12: 372-385. [DOI:10.1111/j.1462-5822.2009.01404.x]
13. Kaur P, Nagaraja GM, Zheng H, Gizachew D, Galukande M, Krishnan S, et al. A mouse model for triple-negative breast cancer tumor-initiating cells (TNBC-TICs) exhibits similar aggressive phenotype to the human disease. BMC cancer 2012; 12: 120. [DOI:10.1186/1471-2407- 12-120]
14. Kim J-H, Jeun E-J, Hong C-P, Kim S-H, Jang MS, Lee E-J, et al. Extracellular vesicle-derived protein from Bifidobacterium longum alleviates food allergy through mast cell suppression. J Allergy Clin Immunol 2016; 137: 507-516. [DOI:10.1016/j.jaci.2015.08.016]
15. Klimentová J, Stulík J. Methods of isolation and purification of outer membrane vesicles from gram-negative bacteria. Microbiol Res 2015; 170: 1-9. [DOI:10.1016/j.micres.2014.09.006]
16. Kulp A, Kuehn MJ. Biological functions and biogenesis of secreted bacterial outer membrane vesicles. Annu Rev Microbiol 2010; 64: 163-184. [DOI:10.1146/annurev.micro.091208.073413]
17. Kumar P, Aggarwal R. An overview of triple-negative breast cancer. Arch Gynecol Obstet 2016; 293: 247-269. [DOI:10.1007/s00404-015-3859-y]
18. Kunsmann L, Rüter C, Bauwens A, Greune L, Glüder M, Kemper B, et al. Virulence from vesicles: Novel mechanisms of host cell injury by Escherichia coli O104: H4 outbreak strain. Sci Rep 2015; 5: 13252. [DOI:10.1038/srep1325]
19. Li Z-T, Zhang R-L, Bi X-G, Xu L, Fan M, Xie D, et al. Outer membrane vesicles isolated from two clinical Acinetobacter baumannii strains exhibit different toxicity and proteome characteristics. Microb Pathog 2015; 81: 46-52. [DOI:10.1016/j.micpath.2015.03.009]
20. Little TJ, O'Connor B, Colegrave N, Watt K, Read AF. Maternal transfer of strain-specific immunity in an invertebrate. Curr Biol 2003; 13: 489-492. [DOI:10.1016/S0960- 9822(03)00163-5]
21. Liu Y, Yin X, Zhong J, Guan N, Luo Z, Min L, et al. Systematic identification and assessment of therapeutic targets for breast cancer based on genome-wide RNA interference transcriptomes. Genes 2017; 8: 86. [DOI:10.3390/genes8030086]
22. Martin TA, Ye L, Sanders AJ, Lane J, Jiang WG. Cancer invasion and metastasis: molecular and cellular perspective. Madame Curie Bioscience Database [Internet]: Landes Bioscience, 2013.
23. McBroom AJ, Kuehn MJ. Release of outer membrane vesicles by Gram‐negative bacteria is a novel envelope stress response. Mol Microbiol 2007; 63: 545-558. [DOI:10.1111/j.1365- 2958.2006.05522.x]
24. Mondal A, Tapader R, Chatterjee NS, Ghosh A, Sinha R, Koley H, et al. Cytotoxic and inflammatory responses induced by outer membrane vesicle-associated biologically active proteases from Vibrio cholerae. Infect Immun 2016; 84: 1478-1490. [DOI:10.1128/IAI.01365-15]
25. Pappas K, Xu J, Zairis S, Resnick-Silverman L, Abate F, Steinbach N, et al. p53 maintains baseline expression of multiple tumor suppressor genes. Mol Cancer Res 2017; 15: 1051-1062. [DOI:10.1158/1541-7786.MCR-17-0089]
26. Parise C, Caggiano V. The influence of marital status and race/ethnicity on risk of mortality for triple negative breast cancer. PloS one 2018; 13: e0196134. [DOI:10.1371/journal.pone.0196134]
27. Pommier Y, Leo E, Zhang H, Marchand C. DNA topoisomerases and their poisoning by anticancer and antibacterial drugs. Chem Biol 2010; 17: 421-433. [DOI:10.1016/j.chembiol.2010.04.012]
28. Pope TM. New Regulations Require Better Communication With Patients Who Have Disabilities and Limited English Proficiency. ASCO Post (January 25, 2019) 2019.
29. Ranjbar S, Seyednejad SA, Azimi H, Rezaeizadeh H, Rahimi R. Emerging Roles of Probiotics in Prevention and Treatment of Breast Cancer: A Comprehensive Review of Their Therapeutic Potential. Nutr Cancer 2019: 1-12. [DOI:10.1080/01635581.2018.1557221]
30. Saber A, Alipour B, Faghfoori Z, Yari Khosroushahi A. Cellular and molecular effects of yeast probiotics on cancer. Crit Rev Microbiol 2017; 43: 96-115. [DOI:10.1080/1040841X.2016.1179622]
31. Shahidi S, Jamili S, Mostafavi PG, Rezaie S, Khorramizadeh M. Assessment of the Inhibitory Effects of Ficin-hydrolyzed Gelatin Derived from Squid (Uroteuthis duvauceli) on Breast Cancer Cell Lines and Animal Model. Iran J Allergy Asthma Immunol 2018; 17: 436-452. [DOI:10.18502/ijaai.v17i5.302]
32. Tacar O, Sriamornsak P, Dass CR. Doxorubicin: an update on anticancer molecular action, toxicity and novel drug delivery systems. J Pharm Pharmacol 2013; 65: 157-170. [DOI:10.1111/j.2042-7158.2012.01567.x]
33. Tao K, Fang M, Alroy J, Sahagian GG. Imagable 4T1 model for the study of late stage breast cancer. BMC cancer 2008; 8: 228. [DOI:10.1186/1471-2407-8-228]
34. Tian J, Ran B, Zhang C, Yan D, Li X. Estrogen and progesterone promote breast cancer cell proliferation by inducing cyclin G1 expression. Braz J Med Biol Res 2018; 51: 1-7. [DOI:10.1590/1414-431x20175612 van]
35. Baarlen P, Wells JM, Kleerebezem M. Regulation of intestinal homeostasis and immunity with probiotic lactobacilli. Trends Immunol 2013; 34: 208-215. [DOI:10.1016/]
36. van Zijl F, Krupitza G, Mikulits W. Initial steps of metastasis: cell invasion and endothelial transmigration. Mutat Res Rev Mutat Res 2011; 728: 23-34. [DOI:10.1016/j.mrrev.2011.05.002]
37. Varna M, Lehmann‐Che J, Turpin E, Marangoni E, El‐Bouchtaoui M, Jeanne M, et al. p53 dependent cell‐cycle arrest triggered by chemotherapy in xenografted breast tumors. Int J Cancer 2009; 124: 991-997. [DOI:10.1002/ijc.24049]

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