Preventive and Tumor-Suppressive Effects of Lactobacillus Paracasei X12 in Rat Model of Colorectal Cancer

Document Type : Research article

Authors

1 Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

2 Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.

3 Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.

4 Department of Pathology, Imam Reza Hospital, Tabriz University of Medical Sciences, Tabriz, Iran.

5 Department of Community Nutrition, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.

Abstract

The paper in hand seeks to evaluate the tumor-suppressive and apoptotic effects of L. paracasei X12 in 1, 2dimethylhydrazine (DMH)-induced rat colon carcinogenesis. The rats were divided into three groups (n = 8-12 per group); L. paracasei X12 was administrated to these animals for forty weeks. The fndings of this study indicated that L. paracasei X12 administration prevented severe weight loss in DMH-treated rats. It was also determined that L. paracasei X12 administration could prevent the neoplasia incidence, cell proliferation and it also could suppress the tumors’ growth. Additionally, a signifcant improvement was observed in apoptosis indexes and cell proliferation in probiotic-treated rats. In conclusion, this study provides insights into the therapeutic potential of L. paracasei X12 with emphasis on the issue that modulation of apoptosis pathway could leave benefcial effects in the prevention and suppression of colorectal cancer (CRC). However, further studies are in support to clarify the mechanisms involved in the tumor-suppressive effect of probiotics.

Graphical Abstract

Preventive and Tumor-Suppressive Effects of Lactobacillus Paracasei X12 in Rat Model of Colorectal Cancer

Keywords


(1)        Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A and Bray F. Global patterns and trends in colorectal cancer incidence and mortality. Gut (2017) 66: 683-91.
(2)        Siegel R, DeSantis C and Jemal A. Colorectal cancer statistics, 2014. CA Cancer J. Clin. (2014) 64: 104-17.
(3)        Shreiner AB, Kao JY and Young VB. The gut microbiome in health and in disease. Curr. Opin. Gastroenterol. (2015) 31: 69-75.
(4)        DuPont AW and DuPont HL. The intestinal microbiota and chronic disorders of the gut. Nat. Rev. Gastroenterol. Hepatol. (2011) 8: 523-31.
(5)        Hosseinifard E-S, Morshedi M, Bavafa-Valenlia K, and Saghafi-Asl M. The novel insight into anti-inflammatory and anxiolytic effects of psychobiotics in diabetic rats: possible link between gut microbiota and brain regions. Eur. J. Nutr. (2019) 3361-75.
(6)        Davis CD and Milner JA. Gastrointestinal microflora, food components and colon cancer prevention. J. Nutr. Biochem. (2009) 20: 743-52.
(7)        Marchesi JR, Dutilh BE, Hall N, Peters WH, Roelofs R, Boleij A and Tjalsma H. Towards the human colorectal cancer microbiome. PLoS One (2011) 6: e20447.
(8)        Sobhani I, Tap J, Roudot-Thoraval F, Roperch JP, Letulle S, Langella P, Corthier G, Van Nhieu JT and Furet JP. Microbial dysbiosis in colorectal cancer (CRC) patients. PLoS One (2011) 6: e16393.
(9)        Morshedi M, Valenlia KB, Hosseinifard ES, Shahabi P, Abbasi MM, Ghorbani M, Barzegari A, Sadigh-Eteghad S and Saghafi-Asl M. Beneficial psychological effects of novel psychobiotics in diabetic rats: the interaction among the gut, blood, and amygdala. J. Nutr. Biochem. (2018) 57: 145-52.
(10)      Aureli P, Capurso L, Castellazzi AM, Clerici M, Giovannini M, Morelli L, Poli A, Pregliasco F, Salvini F and Zuccotti GV. Probiotics and health: an evidence-based review. Pharmacol. Res. (2011) 63: 366-76.
(11)      Valenlia KB, Morshedi M, Saghafi-Asl M, Shahabi P and Abbasi MM. Beneficial impacts of Lactobacillus plantarum and inulin on hypothalamic levels of insulin, leptin, and oxidative markers in diabetic rats. J. Funct. Foods. (2018) 46: 529-37.
(12)      Gamallat Y, Ren X, Walana W, Meyiah A, Xinxiu R, Zhu Y, Li M, Song S, Xie L and Jamalat Y. Probiotic Lactobacillus rhamnosus modulates the gut microbiome composition attenuates preneoplastic colorectal Aberrant crypt foci. J. Funct. Foods (2019) 53: 146-56.
(13)      Shadnoush M, Hosseini RS, Mehrabi Y, Delpisheh A, Alipoor E, Faghfoori Z, Mohammadpour N and Moghadam JZ. Probiotic yogurt affects pro-and anti-inflammatory factors in patients with inflammatory bowel disease. Iran. J. Pharm. Res. (2013) 12: 929-36.
(14)      Chua KJ, Kwok WC, Aggarwal N, Sun T and Chang MW. Designer probiotics for the prevention and treatment of human diseases. Curr. Opin. Chem. Biol. (2017) 40: 8-16.
(15)      Chen CC, Lin WC, Kong MS, Shi HN, Walker WA, Lin CY, Huang CT, Lin YC, Jung SM and Lin TY. Oral inoculation of probiotics Lactobacillus acidophilus NCFM suppresses tumour growth both in segmental orthotopic colon cancer and extra-intestinal tissue. Br. J. Nutr. (2012) 107: 1623-34.
(16)      Capurso G, Marignani M and Delle Fave G. Probiotics and the incidence of colorectal cancer: when evidence is not evident. Dig. Liver. Dis. (2006) 38: S277-S82.
(17)      Konishi H, Fujiya M, Tanaka H, Ueno N, Moriichi K, Sasajima J, Ikuta K, Akutsu H, Tanabe H and Kohgo Y. Probiotic-derived ferrichrome inhibits colon cancer progression via JNK-mediated apoptosis. Nat. Commun. (2016) 7: 1-12.
(18)      Jan G, Belzacq A, Haouzi D, Rouault A, Metivier D, Kroemer G and Brenner C. Propionibacteria induce apoptosis of colorectal carcinoma cells via short-chain fatty acids acting on mitochondria. Cell Death. Differ. (2002) 9: 179-88.
(19)      Tsai T-L, Li AC, Chen YC, Liao YS and Lin T-H. Antimicrobial peptide m2163 or m2386 identified from Lactobacillus casei ATCC 334 can trigger apoptosis in the human colorectal cancer cell line SW480. Tumor Biol. (2015) 36: 3775-89.
(20)      Faghfoori Z, Gargari BP, Saber A, Seyyedi M and Khosroushahi AY. The investigation of the diversity of lactobacilli spp. and assessment their some probiotic properties in traditional dairy products in East Azerbaijan province in Iran. Iran. J. pharm. Res. (2017) 16: 1538-45.
(21)      Faghfoori Z, Gargari BP, Gharamaleki AS, Bagherpour H and Khosroushahi AY. Cellular and molecular mechanisms of probiotics effects on colorectal cancer. J. Funct. Foods (2015) 18: 463-72.
(22)      Arthur JC, Gharaibeh RZ, Uronis JM, Perez-Chanona E, Sha W, Tomkovich S, Mühlbauer M, Fodor AA and Jobin C. VSL# 3 probiotic modifies mucosal microbial composition but does not reduce colitis-associated colorectal cancer. Sci. Rep. (2013) 3: 1-9.
(23)      Gamallat Y, Meyiah A, Kuugbee ED, Hago AM, Chiwala G, Awadasseid A, Bamba D, Zhang X, Shang X and Luo F. Lactobacillus rhamnosus induced epithelial cell apoptosis, ameliorates inflammation and prevents colon cancer development in an animal model. Biomed. Pharmacother. (2016) 83: 536-41.
(24)      Maia LP, Levi YLdAS, do Prado RL, dos Santos Santinoni C and Marsicano JA. Effects of probiotic therapy on serum inflammatory markers: A systematic review and meta-analysis. J. Funct. Foods (2019) 54: 466-78.
(25)      Pagnini C, Saeed R, Bamias G, Arseneau KO, Pizarro TT and Cominelli F. Probiotics promote gut health through stimulation of epithelial innate immunity. Proc. Natl. Acad. Sci. (2009) 107: 454-59.
(26)      Zhu Y, Luo TM, Jobin C and Young HA. Gut microbiota and probiotics in colon tumorigenesis. Cancer Lett. (2011) 309: 119-27.
(27)      Paolillo R, Carratelli CR, Sorrentino S, Mazzola N and Rizzo A. Immunomodulatory effects of Lactobacillus plantarum on human colon cancer cells. Int. Immunopharmacol. (2009) 9: 1265-71.
(28)      Zhang Jy, Xiao X, Dong Y, Wu J, Yao F and Zhou Xh. Effect of fermented wheat germ extract with lactobacillus plantarum dy-1 on HT-29 cell proliferation and apoptosis. J. Agric. Food Chem. (2015) 63: 2449-57.
(29)      Wong RS. Apoptosis in cancer: from pathogenesis to treatment. J. Exp. Clin. Cancer Res. (2011) 30: 87.
(30)      Sharma S, Singh R and Kakkar P. Modulation of Bax/Bcl-2 and caspases by probiotics during acetaminophen induced apoptosis in primary hepatocytes. Food Chem. Toxicol. (2011) 49: 770-9.
(31)      Rizzardini G, Eskesen D, Calder PC, Capetti A, Jespersen L and Clerici M. Evaluation of the immune benefits of two probiotic strains Bifidobacterium animalis ssp. lactis, BB-12® and Lactobacillus paracasei ssp. paracasei, L. casei 431® in an influenza vaccination model: a randomised, double-blind, placebo-controlled study. Br. J. Nutr. (2012) 107: 876-84.
(32)      Wang J, Tang H, Zhang C, Zhao Y, Derrien M, Rocher E, Vlieg JEv-H, Strissel K, Zhao L and Obin M. Modulation of gut microbiota during probiotic-mediated attenuation of metabolic syndrome in high fat diet-fed mice. ISME J. (2015) 9: 1-15.
(33)      Paturi G, Phillips M, Jones M and Kailasapathy K. Immune enhancing effects of Lactobacillus acidophilus LAFTI L10 and Lactobacillus paracasei LAFTI L26 in mice. Int. J. Food Microbiol. (2007) 115: 115-8.
(34)      Faghfoori Z, Pourghassem Gargari B, Saber A, Seyyedi M, Fazelian S and Yari Khosroushahi A. Prophylactic effects of secretion metabolites of dairy lactobacilli through downregulation of ErbB-2 and ErbB-3 genes on colon cancer cells. Eur. J. Cancer Prev. (2017) 29: 201-9.
(35)      Zhang M, Fan X, Fang B, Zhu C, Zhu J and Ren F. Effects of Lactobacillus salivarius Ren on cancer prevention and intestinal microbiota in 1, 2-dimethylhydrazine-induced rat model. J. Microbiol. (2015) 53: 398-405.
(36)      Huang L, Shan YJ, He CX, Ren M-H, Tian PJ and Song W. Effects of L. paracasei subp. paracasei X12 on cell cycle of colon cancer HT-29 cells and regulation of mTOR signalling pathway. J. Funct. Foods. (2016) 21: 431-9.
(37)      Hamilton SR and Aaltonen LA, Pathology and genetics of tumours of the digestive system. Vol. 48. 2000: IARC press Lyon.
(38)      Li W and Li C-B. Effect of oral Lactococcus lactis containing endostatin on 1, 2-dimethylhydrazine-induced colon tumor in rats. World J. Gastroenterol. (2005) 11: 7242-7.
(39)      Cederholm TE, Bauer JM, Boirie Y, Schneider SM, Sieber CC and Rolland Y. Toward a definition of sarcopenia. Clin. Geriatr. Med. (2011) 27: 341-53.
(40)      Miyamoto Y, Baba Y, Sakamoto Y, Ohuchi M, Tokunaga R, Kurashige J, Hiyoshi Y, Iwagami S, Yoshida N and Yoshida M. Sarcopenia is a negative prognostic factor after curative resection of colorectal cancer. Ann. Surg. Oncol. (2015) 22: 2663-8.
(41)      Marzetti E, Calvani R, Cesari M, Buford TW, Lorenzi M, Behnke BJ and Leeuwenburgh C. Mitochondrial dysfunction and sarcopenia of aging: from signaling pathways to clinical trials. Int. J. Biochem. Cell Biol. (2013) 45: 2288-301.
(42)      Xue X, Bredell BX, Anderson ER, Martin A, Mays C, Nagao Kitamoto H, Huang S, Győrffy B, Greenson JK and Hardiman K. Quantitative proteomics identifies STEAP4 as a critical regulator of mitochondrial dysfunction linking inflammation and colon cancer. Proc. Natl. Acad. Sci. (2017) 114: E9608-E9617.
(43)      Walia S, Kamal R, Kanwar SS and Dhawan DK. Cyclooxygenase as a target in chemoprevention by probiotics during 1, 2-dimethylhydrazine induced colon carcinogenesis in rats. Nutr. Cancer (2015) 67: 603-11.
(44)      Yeh KY, Wang HM, Chang JWC, Huang JS, Lai CH, Lan YJ, Wu TH, Chang PH, Wang H and Wu CJ. Omega-3 fatty acid-, micronutrient-, and probiotic-enriched nutrition helps body weight stabilization in head and neck cancer cachexia. Oral Surg. Oral Med. Oral Pathol. Oral. Radiol. (2013) 116: 41-8.
(45)      Grimoud J, Durand H, De Souza S, Monsan P, Ouarné F, Theodorou V and Roques CJIjofm. In-vitro screening of probiotics and synbiotics according to anti-inflammatory and anti-proliferative effects. Int. J. Food Microbiol. (2010) 144: 42-50.
(46)      Andreasen AS, Larsen N, Pedersen Skovsgaard T, Berg RM, Møller K, Svendsen KD, Jakobsen M and Pedersen BK. Effects of Lactobacillus acidophilus NCFM on insulin sensitivity and the systemic inflammatory response in human subjects. Br. J. Nutr. (2010) 104: 1831-8.
(47)      Rinne M, Kalliomaki M, Arvilommi H, Salminen S and Isolauri E. Effect of probiotics and breastfeeding on the bifidobacterium and lactobacillus/enterococcus microbiota and humoral immune responses. J. Pediatr. (2005) 147: 186-91.
(48)      Carasi P, Racedo SM, Jacquot C, Romanin DE, Serradell M and Urdaci M. Impact of kefir derived Lactobacillus kefiri on the mucosal immune response and gut microbiota. J. Immunol. Res. (2015) 2015: 2015.
(49)      Hemarajata P and Versalovic J. Effects of probiotics on gut microbiota: mechanisms of intestinal immunomodulation and neuromodulation. Therap. Adv. Gastroenterol. (2013) 6: 39-51.
(50)      Axling U, Olsson C, Xu J, Fernandez C, Larsson S, Ström K, Ahrné S, Holm C, Molin G and Berger K. Green tea powder and Lactobacillus plantarum affect gut microbiota, lipid metabolism and inflammation in high-fat fed C57BL/6J mice. Nutr. Metab. (2012) 9: 105-22.
(51)      Anderson RC, Cookson AL, McNabb WC, Park Z, McCann MJ, Kelly WJ and Roy NC. Lactobacillus plantarum MB452 enhances the function of the intestinal barrier by increasing the expression levels of genes involved in tight junction formation. BMC Microbiol. (2010) 10: 316.
(52)      Louis P, Hold GL and Flint HJ. The gut microbiota, bacterial metabolites and colorectal cancer. Nat. Rev. Microbiol. (2014) 12: 661-72.
(53)      Lévy J, Cacheux W, Bara MA, L’Hermitte A, Lepage P, Fraudeau M, Trentesaux C, Lemarchand J, Durand A and Crain A-M. Intestinal inhibition of Atg7 prevents tumour initiation through a microbiome-influenced immune response and suppresses tumour growth. Nat. Cell. Biol. (2015) 17: 1062-73.
(54)      Evan GI and Vousden KH. Proliferation, cell cycle and apoptosis in cancer. Nature. (2001) 411: 342-8.
(55)      Arthur JC, Gharaibeh RZ, Uronis JM, Perez Chanona E, Sha W, Tomkovich S, Mühlbauer 11M, Fodor AA and Jobin C. VSL#3 probiotic modifies mucosal microbial composition but does not reduce colitis-associated colorectal cancer. Sc.i Rep. (2013) 3: 2868-76.
(56)      Saber A, Alipour B, Faghfoori Z and Yari Khosroushahi A. Cellular and molecular effects of yeast probiotics on cancer. Crit. Rev. Microbiol. (2017) 43: 96-115.
(57)      Saber A, Alipour B, Faghfoori Z, Mousavi Jam A and Yari Khosroushahi A. Secretion metabolites of probiotic yeast, Pichia kudriavzevii AS-12, induces apoptosis pathways in human colorectal cancer cell lines. Nutr. Res. (2017) 41: 36-46.
(58)      Faghfoori Z, Pourghassem Gargari B, Saber A, Seyyedi M, Fazelian S and Yari Khosroushahi A. Prophylactic effects of secretion metabolites of dairy lactobacilli through downregulation of ErbB-2 and ErbB-3 genes on colon cancer cells. Eur. J. Cancer Prev. (2020) 29: 201-9.
(59)      Reed JC. Bcl-2 family proteins: regulators of apoptosis and chemoresistance in hematologic malignancies. Semin. Hematol. (1997) 34: 9-19.
(60)      Kim SY, Kim JY, Kim SH, Bae HJ, Yi H, Yoon SH, Koo BS, Kwon M, Cho JY, Lee CE and Hong S. Surfactin from Bacillus subtilis displays anti-proliferative effect via apoptosis induction, cell cycle arrest and survival signaling suppression. FEBS Lett. (2007) 581: 865-71.
(61)      Xiong H, Zhang ZG, Tian XQ, Sun DF, Liang QC, Zhang YJ, Lu R, Chen YX and Fang JY. Inhibition of JAK1, 2/STAT3 signaling induces apoptosis, cell cycle arrest, and reduces tumor cell invasion in colorectal cancer cells. Neoplasia. (2008) 10: 287-97.
(62)      Ma XT, Wang S, Ye YJ, Du RY, Cui ZR and Somsouk M. Constitutive activation of Stat3 signaling pathway in human colorectal carcinoma. World J. Gastroenterol. (2004) 10: 1569-73.
(63)      Blaskovich MA, Sun J, Cantor A, Turkson J, Jove R and Sebti SM. Discovery of JSI-124 (cucurbitacin I), a selective Janus kinase/signal transducer and activator of transcription 3 signaling pathway inhibitor with potent antitumor activity against human and murine cancer cells in mice. Cancer Res. (2003) 63: 1270-9.
(64)      Tiptiri-Kourpeti A, Spyridopoulou K, Santarmaki V, Aindelis G, Tompoulidou E, Lamprianidou EE, Saxami G, Ypsilantis P, Lampri ES and Simopoulos C. Lactobacillus casei exerts anti-proliferative effects accompanied by apoptotic cell death and up-regulation of TRAIL in colon carcinoma cells. PLoS One (2016) 11: e0147960.
(65)      Saxami G, Karapetsas A, Lamprianidou E, Kotsianidis I, Chlichlia A, Tassou C, Zoumpourlis V and Galanis AJJoFF. Two potential probiotic lactobacillus strains isolated from olive microbiota exhibit adhesion and anti-proliferative effects in cancer cell lines. J. Funct. Foods. (2016) 24: 461-71.