Kefir: A Synbiotic with Approved Anticarcinogenic Properties

Article ID: e010621189545 Pages: 9

  • * (Excluding Mailing and Handling)

Abstract

Background: According to WHO report, cancer is the second leading cause of death globally, and approximately 70% of deaths from cancer occur in low- and middle-income countries. From this point, more attention has been given to the role of nutrition in the prevention of cancer development.

Methods: A structured search of bibliographic databases for peer-reviewed research literature dealing with the role of kefir in cancer prevention and treatment was undertaken.

Results: Probiotics are one of the most important food fortifications which are proved to have anticarcinogenic properties. Probiotics can directly bind to carcinogens and alter the production of enzymes by modifying the intestinal environment. Kefir, originating from the Balkan–Caucasian region, is a synbiotic composed of a wide number microflora and exopolysaccharides with approved in vitro and in vivo biological activities. Kefir plays a great potential role in cancer prevention and treatment, interfering with apoptosis, proliferation and transformation.

Conclusion: This review highlights the important role of probiotics, exopolysaccharides and common kefir in preventing different types of cancer, including colon cancer, sarcoma, breast cancer, lung cancer, leukemia, gastric cancer and melanoma.

Keywords: Cancer, kefir, probiotics, exopolysaccharides, apoptosis, proliferation.

Graphical Abstract

[1]
Sharifi, M.; Moridnia, A.; Mortazavi, D.; Salehi, M.; Bagheri, M.; Sheikhi, A. Kefir: a powerful probiotics with anticancer properties. Med. Oncol., 2017, 34(11), 183.
[http://dx.doi.org/10.1007/s12032-017-1044-9] [PMID: 28956261]
[2]
John, S.M.; Deeseenthum, S. Properties and benefits of kefir -A review. Songklanakarin J. Sci. Technol., 2015, 37(3), 275-282.
[3]
Rosa, D.D.; Dias, M.M.S.; Grześkowiak, Ł.M.; Reis, S.A.; Conceição, L.L.; Peluzio, M.D.C.G. Milk kefir: nutritional, microbiological and health benefits. Nutr. Res. Rev., 2017, 30(1), 82-96.
[http://dx.doi.org/10.1017/S0954422416000275] [PMID: 28222814]
[4]
Kumar, A.S.; Mody, K.; Jha, B. Bacterial exopolysaccharides- a perception. J. Basic Microbiol., 2007, 47(2), 103-117.
[http://dx.doi.org/10.1002/jobm.200610203] [PMID: 17440912]
[5]
Sanlibaba, P.; Çakmak, G.A. Exopolysaccharides production by lactic acid bacteria. Appli Micro Open Access, 2016, 2(2)
[6]
Garrote, G.L.; Abraham, A.G.; De Antoni, G.L. Microbial interactions in Kefir: a natural probiotic drink.Biotechnology of lactic acid bacteria: novel applications; Wiley-Blackwell, 2010, pp. 327-336.
[http://dx.doi.org/10.1002/9780813820866.ch18]
[7]
FAO/WHO. Guidelines for the Evaluation of Probiotics in Food. Joint FAO/WHO Working Group Report on Drafting Guidelines for the Evaluation of Probiotics in Food. London, Ontario, 2002.
[8]
Sikorska, H.; Smoragiewicz, W. Role of probiotics in the prevention and treatment of meticillin-resistant Staphylococcus aureus infections. Int. J. Antimicrob. Agents, 2013, 42(6), 475-481.
[http://dx.doi.org/10.1016/j.ijantimicag.2013.08.003] [PMID: 24071026]
[9]
Tappenden, K.A.; Deutsch, A.S. The physiological relevance of the intestinal microbiota- contributions to human health. J. Am. Coll. Nutr., 2007, 26(6), 679S-683S.
[http://dx.doi.org/10.1080/07315724.2007.10719647] [PMID: 18187433]
[10]
Ebert, M.N.; Klinder, A.; Peters, W.H.; Schäferhenrich, A.; Sendt, W.; Scheele, J.; Pool-Zobel, B.L. Expression of glutathione S- transferases (GSTs) in human colon cells and inducibility of GSTM2 by butyrate. Carcinogenesis, 2003, 24(10), 1637-1644.
[http://dx.doi.org/10.1093/carcin/bgg122] [PMID: 12896903]
[11]
Ewaschuk, J.B.; Walker, J.W.; Diaz, H.; Madsen, K.L. Bioproduction of conjugated linoleic acid by probiotic bacteria occurs in vitro and in vivo in mice. J. Nutr., 2006, 136(6), 1483-1487.
[http://dx.doi.org/10.1093/jn/136.6.1483] [PMID: 16702308]
[12]
Motevaseli, E.; Dianatpour, A.; Ghafouri-Fard, S. The role of probiotics in cancer treatment: Emphasis on their in vivo and in vitro anti-metastatic effects. Int. J. Mol. Cell. Med., 2017, 6(2), 66-76.
[PMID: 28890883]
[13]
Sunkata, R.; Herring, J.; Walker, L.T.; Verghese, M. Chemopreventive Potential of Probiotics and Prebiotics. Food Nutr. Sci., 2014, 5, 1800-1809.
[http://dx.doi.org/10.4236/fns.2014.518194]
[14]
de Moreno de LeBlanc, A.; Perdigón, G. Reduction of beta-glucuronidase and nitroreductase activity by yoghurt in a murine colon cancer model. Biocell, 2005, 29(1), 15-24.
[PMID: 15954463]
[15]
El-Nezami, H.S.; Polychronaki, N.N.; Ma, J.; Zhu, H.; Ling, W.; Salminen, E.K.; Juvonen, R.O.; Salminen, S.J.; Poussa, T.; Mykkänen, H.M. Probiotic supplementation reduces a biomarker for increased risk of liver cancer in young men from Southern China. Am. J. Clin. Nutr., 2006, 83(5), 1199-1203.
[http://dx.doi.org/10.1093/ajcn/83.5.1199] [PMID: 16685066]
[16]
Rafter, J.; Bennett, M.; Caderni, G.; Clune, Y.; Hughes, R.; Karlsson, P.C.; Klinder, A.; O’Riordan, M.; O’Sullivan, G.C.; Pool-Zobel, B.; Rechkemmer, G.; Roller, M.; Rowland, I.; Salvadori, M.; Thijs, H.; Van Loo, J.; Watzl, B.; Collins, J.K. Dietary synbiotics reduce cancer risk factors in polypectomized and colon cancer patients. Am. J. Clin. Nutr., 2007, 85(2), 488-496.
[http://dx.doi.org/10.1093/ajcn/85.2.488] [PMID: 17284748]
[17]
Hatakka, K.; Holma, R.; El-Nezami, H.; Suomalainen, T.; Kuisma, M.; Saxelin, M.; Poussa, T.; Mykkänen, H.; Korpela, R. The influence of Lactobacillus rhamnosus LC705 together with Propionibacterium freudenreichii ssp. shermanii JS on potentially carcinogenic bacterial activity in human colon. Int. J. Food Microbiol., 2008, 128(2), 406-410.
[http://dx.doi.org/10.1016/j.ijfoodmicro.2008.09.010] [PMID: 18945506]
[18]
Brady, L.J.; Gallaher, D.D.; Busta, F.F. The role of probiotic cultures in the prevention of colon cancer. J. Nutr., 2000, 130(2S)(Suppl.), 410S-414S.
[http://dx.doi.org/10.1093/jn/130.2.410S] [PMID: 10721916]
[19]
Kumar, R.S.; Kanmani, P.; Yuvaraj, N.; Paari, K.A.; Pattukumar, V.; Thirunavukkarasu, C.; Arul, V. Lactobacillus plantarum AS1 isolated from south Indian fermented food Kallappam suppress 1,2-dimethyl hydrazine (DMH)-induced colorectal cancer in male Wistar rats. Appl. Biochem. Biotechnol., 2012, 166(3), 620-631.
[http://dx.doi.org/10.1007/s12010-011-9453-2] [PMID: 22161238]
[20]
Orlando, A.; Refolo, M.G.; Messa, C.; Amati, L.; Lavermicocca, P.; Guerra, V.; Russo, F. Antiproliferative and proapoptotic effects of viable or heat-killed Lactobacillus paracasei IMPC2.1 and Lactobacillus rhamnosus GG in HGC-27 gastric and DLD-1 colon cell lines. Nutr. Cancer, 2012, 64(7), 1103-1111.
[http://dx.doi.org/10.1080/01635581.2012.717676] [PMID: 23061912]
[21]
Lee, J.W.; Shin, J.G.; Kim, E.H.; Kang, H.E.; Yim, I.B.; Kim, J.Y.; Joo, H.G.; Woo, H.J. Immunomodulatory and antitumor effects in vivo by the cytoplasmic fraction of Lactobacillus casei and Bifidobacterium longum. J. Vet. Sci., 2004, 5(1), 41-48.
[http://dx.doi.org/10.4142/jvs.2004.5.1.41] [PMID: 15028884]
[22]
Azam, R.; Ghafouri-Fard, S.; Tabrizi, M.; Modarressi, M.H.; Ebrahimzadeh-Vesal, R.; Daneshvar, M.; Mobasheri, M.B.; Motevaseli, E. Lactobacillus acidophilus and Lactobacillus crispatus culture supernatants downregulate expression of cancer-testis genes in the MDA-MB-231 cell line. Asian Pac. J. Cancer Prev., 2014, 15(10), 4255-4259.
[http://dx.doi.org/10.7314/APJCP.2014.15.10.4255] [PMID: 24935380]
[23]
Ogawa, J.; Kishino, S.; Ando, A.; Sugimoto, S.; Mihara, K.; Shimizu, S. Production of conjugated fatty acids by lactic acid bacteria. J. Biosci. Bioeng., 2005, 100(4), 355-364.
[http://dx.doi.org/10.1263/jbb.100.355] [PMID: 16310724]
[24]
McCarty, M.F. Activation of PPARgamma may mediate a portion of the anticancer activity of conjugated linoleic acid. Med. Hypotheses, 2000, 55(3), 187-188.
[http://dx.doi.org/10.1054/mehy.1999.1010] [PMID: 10985906]
[25]
Tontonoz, P.; Hu, E.; Spiegelman, B.M. Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor. Cell, 1994, 79(7), 1147-1156.
[http://dx.doi.org/10.1016/0092-8674(94)90006-X] [PMID: 8001151]
[26]
Kitamura, S.; Miyazaki, Y.; Shinomura, Y.; Kondo, S.; Kanayama, S.; Matsuzawa, Y. Peroxisome proliferator-activated receptor gamma induces growth arrest and differentiation markers of human colon cancer cells. Jpn. J. Cancer Res., 1999, 90(1), 75-80.
[http://dx.doi.org/10.1111/j.1349-7006.1999.tb00668.x] [PMID: 10076568]
[27]
Elstner, E.; Müller, C.; Koshizuka, K.; Williamson, E.A.; Park, D.; Asou, H.; Shintaku, P.; Said, J.W.; Heber, D.; Koeffler, H.P. Ligands for peroxisome proliferator-activated receptorgamma and retinoic acid receptor inhibit growth and induce apoptosis of human breast cancer cells in vitro and in BNX mice. Proc. Natl. Acad. Sci. USA, 1998, 95(15), 8806-8811.
[http://dx.doi.org/10.1073/pnas.95.15.8806] [PMID: 9671760]
[28]
Kubota, T.; Koshizuka, K.; Williamson, E.A.; Asou, H.; Said, J.W.; Holden, S.; Miyoshi, I.; Koeffler, H.P. Ligand for peroxisome proliferator-activated receptor gamma (troglitazone) has potent antitumor effect against human prostate cancer both in vitro and in vivo. Cancer Res., 1998, 58(15), 3344-3352.
[PMID: 9699665]
[29]
Yoshida, K.; Hirose, Y.; Tanaka, T.; Yamada, Y.; Kuno, T.; Kohno, H.; Katayama, M.; Qiao, Z.; Sakata, K.; Sugie, S.; Shibata, T.; Mori, H. Inhibitory effects of troglitazone, a peroxisome proliferator-activated receptor gamma ligand, in rat tongue carcinogenesis initiated with 4-nitroquinoline 1-oxide. Cancer Sci., 2003, 94(4), 365-371.
[http://dx.doi.org/10.1111/j.1349-7006.2003.tb01448.x] [PMID: 12824906]
[30]
Yang, W.L.; Frucht, H. Activation of the PPAR pathway induces apoptosis and COX-2 inhibition in HT-29 human colon cancer cells. Carcinogenesis, 2001, 22(9), 1379-1383.
[http://dx.doi.org/10.1093/carcin/22.9.1379] [PMID: 11532858]
[31]
Beppu, F.; Hosokawa, M.; Tanaka, L.; Kohno, H.; Tanaka, T.; Miyashita, K. Potent inhibitory effect of trans9, trans11 isomer of conjugated linoleic acid on the growth of human colon cancer cells. J. Nutr. Biochem., 2006, 17(12), 830-836.
[http://dx.doi.org/10.1016/j.jnutbio.2006.01.007] [PMID: 16563722]
[32]
Plessas, S.; Nouska, C.; Mantzourani, I.; Kourkoutas, Y.; Alexopoulos, A.; Bezirtzoglou, E. Microbiological exploration of different types of kefir grains. Fermentation, 2006, 3(1), 1-10.
[http://dx.doi.org/10.3390/fermentation3010001]
[33]
Miguel, M.G.C.P.; Magalhães, K.T.; Schwan, R.F. Profile of microbial communities present in tibico (surgary kefir) grains from different Brazilian states. World J. Microbiol. Biotechnol., 2011, 27(8), 1875-1884.
[http://dx.doi.org/10.1007/s11274-010-0646-6]
[34]
Bensmira, M.; Nsabimana, C.; Jiang, B. Effects of fermentation conditions and homogenization pressure on the rheological properties of kefir. Lebensm. Wiss. Technol., 2010, 43(8), 1180-1184.
[http://dx.doi.org/10.1016/j.lwt.2010.04.005]
[35]
Magalhães, K.T.; de Melo Pereira, G.V.; Campos, C.R.; Dragone, G.; Schwan, R.F. Brazilian kefir: structure, microbial communities and chemical composition. Braz. J. Microbiol., 2011, 42(2), 693-702.
[http://dx.doi.org/10.1590/S1517-83822011000200034] [PMID: 24031681]
[36]
De Vuyst, L.; De Vin, F. Exopolysaccharides from lactic acid bacteria.Comprehensive glycol sciences; Elsevier UK, 2007, pp. 477-519.
[http://dx.doi.org/10.1016/B978-044451967-2/00129-X]
[37]
Dailin, D.J.; Elsayed, E.A.; Othman, N.Z.; Malek, R.; Phin, H.S.; Aziz, R.; Wadaan, M.; El Enshasy, H.A. Bioprocess development for kefiran production by Lactobacillus kefiranofaciens in semi industrial scale bioreactor. Saudi J. Biol. Sci., 2016, 23(4), 495-502.
[http://dx.doi.org/10.1016/j.sjbs.2015.06.003] [PMID: 27298582]
[38]
Dailin, D.J.; Elsayed, E.A.; Othman, N.Z.; Abd Malek, R.; Ramli, S.; Sarmidi, M. Development of cultivation medium of high yield kefiran production by lactobacillus kefiranociens. Int. J. Pharm. Pharm. Sci., 2015, 7, 159-163.
[39]
Lee, M.Y.; Ahn, K.S.; Kwon, O.K.; Kim, M.J.; Kim, M.K.; Lee, I.Y.; Oh, S.R.; Lee, H.K. Anti-inflammatory and anti-allergic effects of kefir in a mouse asthma model. Immunobiology, 2007, 212(8), 647-654.
[http://dx.doi.org/10.1016/j.imbio.2007.05.004] [PMID: 17869642]
[40]
Huang, Y.; Wang, X.; Wang, J.; Wu, F.; Sui, Y.; Yang, L.; Wang, Z. Lactobacillus plantarum strains as potential probiotic cultures with cholesterol-lowering activity. J. Dairy Sci., 2013, 96(5), 2746-2753.
[http://dx.doi.org/10.3168/jds.2012-6123] [PMID: 23498020]
[41]
Pogačić, T.; Šinko, S.; Zamberlin, Š.; Samaržija, D. Microbiota of kefir grains. Mljekarstvo, 2013, 63(1), 3-14.
[42]
Lin, C.; Chen, H.; Je-Ruei, L. Identification and characterization of lactic acid bacteria and yeast isolated from kefir grains in Taiwan. Aust. J. Dairy Technol., 1999, 54(1), 14-18.
[43]
Tas, T.K.; Ekinci, F.Y.; Guzel-Seydim, Z.B. Identification of microbial flora in kefir grains produced in Turkey using PCR. Int. J. Dairy Technol., 2012, 65, 126-131.
[http://dx.doi.org/10.1111/j.1471-0307.2011.00733.x]
[44]
Mainville, I.; Robert, N.; Lee, B.; Farnworth, E.R. Polyphasic characterization of the lactic acid bacteria in kefir. Syst. Appl. Microbiol., 2006, 29(1), 59-68.
[http://dx.doi.org/10.1016/j.syapm.2005.07.001] [PMID: 16423657]
[45]
Kotova, I.B.; Cherdyntseva, T.A.; Netrusov, A.I. Russian kefir grains microbial composition and its changes during production process. Adv. Exp. Med. Biol., 2016, 932, 93-121.
[http://dx.doi.org/10.1007/5584_2016_2] [PMID: 27539304]
[46]
Leite, A.M.O.; Mayo, B.; Rachid, C.T.; Peixoto, R.S.; Silva, J.T.; Paschoalin, V.M.F.; Delgado, S. Assessment of the microbial diversity of Brazilian kefir grains by PCR-DGGE and pyrosequencing analysis. Food Microbiol., 2012, 31(2), 215-221.
[http://dx.doi.org/10.1016/j.fm.2012.03.011] [PMID: 22608226]
[47]
Zanirati, D.F.; Abatemarco, M., Jr; Sandes, S.H.C.; Nicoli, J.R.; Nunes, A.C.; Neumann, E. Selection of lactic acid bacteria from Brazilian kefir grains for potential use as starter or probiotic cultures. Anaerobe, 2015, 32, 70-76.
[http://dx.doi.org/10.1016/j.anaerobe.2014.12.007] [PMID: 25542841]
[48]
Gulitz, A.; Stadie, J.; Wenning, M.; Ehrmann, M.A.; Vogel, R.F. The microbial diversity of water kefir. Int. J. Food Microbiol., 2011, 151(3), 284-288.
[http://dx.doi.org/10.1016/j.ijfoodmicro.2011.09.016] [PMID: 22000549]
[49]
Diosma, G.; Romanin, D.E.; Rey-Burusco, M.F.; Londero, A.; Garrote, G.L. Yeasts from kefir grains: isolation, identification, and probiotic characterization. World J. Microbiol. Biotechnol., 2014, 30(1), 43-53.
[http://dx.doi.org/10.1007/s11274-013-1419-9] [PMID: 23824665]
[50]
Garofalo, C.; Osimani, A.; Milanović, V.; Aquilanti, L.; De Filippis, F.; Stellato, G.; Di Mauro, S.; Turchetti, B.; Buzzini, P.; Ercolini, D.; Clementi, F. Bacteria and yeast microbiota in milk kefir grains from different Italian regions. Food Microbiol., 2015, 49, 123-133.
[http://dx.doi.org/10.1016/j.fm.2015.01.017] [PMID: 25846922]
[51]
Fedorov, S.N.; Ermakova, S.P.; Zvyagintseva, T.N.; Stonik, V.A. Anticancer and cancer preventive properties of marine polysaccharides: some results and prospects. Mar. Drugs, 2013, 11(12), 4876-4901.
[http://dx.doi.org/10.3390/md11124876] [PMID: 24317475]
[52]
Kim, Y.; Oh, S.; Yun, H.S.; Oh, S.; Kim, S.H. Cell-bound exopolysaccharide from probiotic bacteria induces autophagic cell death of tumour cells. Lett. Appl. Microbiol., 2010, 51(2), 123-130.
[http://dx.doi.org/10.1111/j.1472-765X.2010.02859.x] [PMID: 20536712]
[53]
Nguyen, D.T.; Nguyen, T.H. Detection on antioxidant and cytotoxicity activities of exopolysaccharides isolated in plant-originated lactococcus lactis. Biomed. Pharmacol. J., 2014, 7(1), 33-38.
[http://dx.doi.org/10.13005/bpj/449]
[54]
Osinska-Jaroszuk, M.; Jaszek, M.; Mizerska-Dudka, M.; Bachowicz, A.; Rejczak, T.; Janusz, G. Exopolysaccharide from ganoderma applanatum as a promising bioactive compound with cytostatic and antibacterial properties. BioMed Research International, 2014.
[55]
Zhou, X.; Hong, T.; Yu, Q.; Nie, S.; Gong, D.; Xiong, T.; Xie, M. Exopolysaccharides from Lactobacillus plantarum NCU116 induce c-Jun dependent Fas/Fasl-mediated apoptosis via TLR2 in mouse intestinal epithelial cancer cells. Sci. Rep., 2017, 7(1), 14247.
[http://dx.doi.org/10.1038/s41598-017-14178-2] [PMID: 29079852]
[56]
Di, W.; Zhang, L.; Yi, H.; Han, X.; Zhang, Y.; Xin, L. Exopolysaccharides produced by Lactobacillus strains suppress HT-29 cell growth via induction of G0/G1 cell cycle arrest and apoptosis. Oncol. Lett., 2018, 16(3), 3577-3586.
[http://dx.doi.org/10.3892/ol.2018.9129] [PMID: 30127964]
[57]
Mahgoub, A.M.; Mahmoud, M.G.; Selim, M.S.; EL Awady, M.E. Exopolysaccharide from Marine Bacillus velezensis MHM3 Induces Apoptosis of Human Breast Cancer MCF-7 Cells through a Mitochondrial Pathway. Asian Pac. J. Cancer Prev., 2018, 19(7), 1957-1963.
[PMID: 30051679]
[58]
Sekkal-Taleb, N. Chemical and microbiological composition of Kefir and its natural benefits. Mediterranean J. Biosci., 2016, 1(4), 174-183.
[59]
Pop, C.R.; Rotar, A.M.; Salanțӑ, L.C.; Semeniuc, C.A. Fingerprint profiling of polysaccharide kefiran extracted from kefir grains biomass. J. Agroalimentary Proc. Tech., 2015, 21(2), 207-212.
[60]
Zajšek, K.; Kolar, M.; Goršek, A. Characterisation of the exopolysaccharide kefiran produced by lactic acid bacteria entrapped within natural kefir grains. Int. J. Dairy Technol., 2011, 64, 544-548.
[http://dx.doi.org/10.1111/j.1471-0307.2011.00704.x]
[61]
Ozcan, A.; Kaya, N.; Atakisi, O.; Karapehlivan, M.; Atakisi, E.; Cenesiz, S. Effect of kefir on the oxidative stress due to lead in rats. J. Appl. Anim. Res., 2009, 35(1), 91-93.
[http://dx.doi.org/10.1080/09712119.2009.9706992]
[62]
Liu, J.R.; Lin, Y.Y.; Chen, M.J.; Chen, L.J.; Lin, C.W. Antioxidative activities of kefir. Asian-Australas. J. Anim. Sci., 2005, 18(4), 567-573.
[http://dx.doi.org/10.5713/ajas.2005.567]
[63]
Díaz-Ropero, M.P.; Martín, R.; Sierra, S.; Lara-Villoslada, F.; Rodríguez, J.M.; Xaus, J.; Olivares, M. Two Lactobacillus strains, isolated from breast milk, differently modulate the immune response. J. Appl. Microbiol., 2007, 102(2), 337-343.
[http://dx.doi.org/10.1111/j.1365-2672.2006.03102.x] [PMID: 17241338]
[64]
Liu, J.R.; Wang, S.Y.; Lin, Y.Y.; Lin, C.W. Antitumor activity of milk kefir and soy milk kefir in tumor-bearing mice. Nutr. Cancer, 2002, 44(2), 183-187.
[http://dx.doi.org/10.1207/S15327914NC4402_10] [PMID: 12734066]
[65]
Tellez, A.; Corredig, M.; Brovko, L.Y.; Griffiths, M.W. Characterization of immune-active peptides obtained from milk fermented by Lactobacillus helveticus. J. Dairy Res., 2010, 77(2), 129-136.
[http://dx.doi.org/10.1017/S002202990999046X] [PMID: 20078905]
[66]
Jain, S.; Yadav, H.; Sinha, P.R.; Marotta, F. Modulation of cytokine gene expression in spleen and Peyer’s patches by feeding dahi containing probiotic Lactobacillus casei in mice. J. Dig. Dis., 2009, 10(1), 49-54.
[http://dx.doi.org/10.1111/j.1751-2980.2008.00362.x] [PMID: 19236547]
[67]
Khoury, N.; El-Hayek, S.; Tarras, O.; El-Sabban, M.; El-Sibai, M.; Rizk, S. Kefir exhibits anti-proliferative and pro-apoptotic effects on colon adenocarcinoma cells with no significant effects on cell migration and invasion. Int. J. Oncol., 2014, 45(5), 2117-2127.
[http://dx.doi.org/10.3892/ijo.2014.2635] [PMID: 25189203]
[68]
Ghoneum, M.; Gimzewski, J. Apoptotic effect of a novel kefir product, PFT, on multidrug-resistant myeloid leukemia cells via a hole-piercing mechanism. Int. J. Oncol., 2014, 44(3), 830-837.
[http://dx.doi.org/10.3892/ijo.2014.2258] [PMID: 24430613]
[69]
Rizk, S.; Maalouf, K.; Baydoun, E. The antiproliferative effect of kefir cell-free fraction on HuT-102 malignant T lymphocytes. Clin. Lymphoma Myeloma, 2009, 9(Suppl. 3), S198-S203.
[http://dx.doi.org/10.3816/CLM.2009.s.012] [PMID: 19778841]
[70]
Grishina, A.; Kulikova, I.; Alieva, L.; Dodson, A.; Rowland, I.; Jin, J. Antigenotoxic effect of kefir and ayran supernatants on fecal water-induced DNA damage in human colon cells. Nutr. Cancer, 2011, 63(1), 73-79.
[PMID: 21161824]
[71]
Alsha'ar, I.A.; Aloklah, B. In vitro anticancer properties of kefir and kefir products produced by a novel method in Syria. Int. J. Pharma. Sci. Invent., 2017, 6, 01-06.
[72]
de Moreno de Leblanc, A.; Matar, C.; Farnworth, E.; Perdigón, G. Study of immune cells involved in the antitumor effect of kefir in a murine breast cancer model. J. Dairy Sci., 2007, 90(4), 1920-1928.
[http://dx.doi.org/10.3168/jds.2006-079] [PMID: 17369232]
[73]
de Moreno de LeBlanc, A.; Matar, C.; Farnworth, E.; Perdigon, G. Study of cytokines involved in the prevention of a murine experimental breast cancer by kefir. Cytokine, 2006, 34(1-2), 1-8.
[http://dx.doi.org/10.1016/j.cyto.2006.03.008] [PMID: 16697655]
[74]
Bourrie, B.C.; Willing, B.P.; Cotter, P.D. The microbiota and health promoting characteristics of the fermented beverage kefir. Front Microbiol, 2016, 17, 647.
[http://dx.doi.org/10.3389/fmicb.2016.00647]
[75]
Furukawa, N.; Matsuoka, A.; Takahashi, T.; Yamanaka, Y. Anti-metastatic effect of kefir grain components on Lewis lung carcinoma and highly metastatic B16 melanoma in mice. J Agric Sci Tokyo, 2000, 45, 62-70.
[76]
Zamberi, N.R.; Abu, N.; Mohamed, N.E.; Nordin, N.; Keong, Y.S.; Beh, B.K.; Zakaria, Z.A.; Nik Abdul Rahman, N.M.; Alitheen, N.B. The antimetastatic and antiangiogenesis effects of kefir water on murine breast cancer cells. Integr. Cancer Ther., 2016, 15(4), NP53-NP66.
[http://dx.doi.org/10.1177/1534735416642862] [PMID: 27230756]
[77]
Murofushi, M.; Mizuguchi, J.; Aibara, K.; Matuhasi, T. Immunopotentiative effect of polysaccharide from kefir grain, KGF-C, administered orally in mice. Immunopharmacology, 1986, 12(1), 29-35.
[http://dx.doi.org/10.1016/0162-3109(86)90049-4] [PMID: 3531087]
[78]
Furukawa, N.; Matsuoka, A.; Yamanaka, Y. Effects of orally administered yoghurt and kefir on tumor growth in mice. J. Jpn. Soc. Nutr. Food Sci., 1990, 43, 450-453.
[http://dx.doi.org/10.4327/jsnfs.43.450]
[79]
Furukawa, N.; Matsuoka, A.; Takahashi, T.; Yamanaka, Y. Effects of fermented milk on the delayed-type hypersensitivity response and survival day in mice bearing Meth-A. Animal Science Technology (Japan), 1991, 62, 579-585.
[80]
Matsuzaki, T.; Yokokura, T.; Mutai, M. The role of lymph node cells in the inhibition of metastasis by subcutaneous injection of Lactobacillus casei in mice. Med. Microbiol. Immunol. (Berl.), 1988, 177(5), 245-253.
[http://dx.doi.org/10.1007/BF00189410] [PMID: 3139973]
[81]
Aragón, F.; Carino, S.; Perdigón, 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(5), 185-196.
[http://dx.doi.org/10.1097/CJI.0000000000000079] [PMID: 25962107]
[82]
Chiu, Y.H.; Hsieh, Y.J.; Liao, K.W.; Peng, K.C. Preferential promotion of apoptosis of monocytes by Lactobacillus casei rhamnosus soluble factors. Clin. Nutr., 2010, 29(1), 131-140.
[http://dx.doi.org/10.1016/j.clnu.2009.07.004] [PMID: 19665262]
[83]
Maalouf, K.; Baydoun, E.; Rizk, S. Kefir induces cell-cycle arrest and apoptosis in HTLV-1-negative malignant T-lymphocytes. Cancer Manag. Res., 2011, 3, 39-47.
[PMID: 21448298]
[84]
Yamane, T.; Sakamoto, T.; Nakagaki, T.; Nakano, Y. Lactic acid bacteria from kefir increase cytotoxicity of natural killer cells to tumor cells. Foods, 2018, 7(4), 48.
[http://dx.doi.org/10.3390/foods7040048] [PMID: 29584690]
[85]
Ghoneum, M.; Felo, N. Selective induction of apoptosis in human gastric cancer cells by Lactobacillus kefiri (PFT), a novel kefir product. Oncol. Rep., 2015, 34(4), 1659-1666.
[http://dx.doi.org/10.3892/or.2015.4180] [PMID: 26251956]
[86]
Gao, J.; Gu, F.; Ruan, H.; Chen, Q.; He, J.; He, G. Induction of apoptosis of gastric cancer cells SGC7901 in vitro by a cell-free fraction of Tibetan kefir. Int. Dairy J., 2013, 30, 14-18.
[http://dx.doi.org/10.1016/j.idairyj.2012.11.011]
[87]
Nagira, T.; Narisawa, J.; Teruya, K.; Katakura, Y.; Shim, S.Y.; Kusumoto, K.; Tokumaru, S.; Tokumaru, K.; Barnes, D.W.; Shirahata, S. Suppression of UVC-induced cell damage and enhancement of DNA repair by the fermented milk, Kefir. Cytotechnology, 2002, 40(1-3), 125-137.
[http://dx.doi.org/10.1023/A:1023984304610] [PMID: 19003113]
[88]
Nagira, T.; Narisawa, J.; Kusumoto, K.; Teruya, K.; Katakura, Y.; Barnes, D.W. Protection of human 1melanoma cells from UV damage by a fermented milk, Kefir. Animal cell technology: Basic and applied aspects; Kitagawa, Y.; Matsuda, T.; Iijima, S., Eds.; Kluwer Academic Publishers: New York, 1999, Vol. 10, pp. 369-373.