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Anti-proliferative, anti-genotoxicity, immunomodulatory, exopolysaccharides, lactic acid bacteria


The third most widespread cancer and the second leading reason for cancer-associated death is colorectal cancer (CRC). Natural agents such as probiotics and postbiotics, that offer anti-carcinogenic effects for CRC prevention, have become an important focus in recent years. Therefore, the aim of this study is to compare the anti-proliferative effects related to anti-genotoxic and immunomodulatory effects of viable probiotics with their exopolysaccharides (EPSs), which is one of their postbiotics. For this purpose, the strains' ability to inhibit the proliferation of HT-29 cells were determined with the WST-1 assay kit, their genotoxic and anti-genotoxic effects with the Comet assay and their immunomodulatory effects with IL-8 and IL-10 ELISA kits. According to our results, both viable probiotics and lyophilized EPSs (L-EPSs) were effective in all studies, but the best anti-proliferative (51% cell death), anti-genotoxic (48% inhibition) and immunomodulatory (for IL-8: 46% suppression and for IL-10: 74% increase) (*p < 0.05) effect was obtained from viable probiotics (Levilactobacillus brevis LB63). Additionally, in the present study found that these effects of L-EPSs were close to viable probiotics. Therefore, it has been shown that postbiotics can be used as alternatively to viable probiotics, because of the properties such as reliable and no side effects of their, thus it may be a useful alternative for cancer. According to these results, new agents such as probiotic-based postbiotics will be introduced to the pharmaceutical and food industry as well as probiotic bacteria that are protective and/or therapeutic against cancer.


Torre, L. A., Bray, F., Siegel, R. L., Ferlay, J., Lortet‐Tieulent, J., Jemal, A. (2015): Global cancer statistics 2012. CA: A Cancer Journal for Clinicians 65(2): 87-108.

American Cancer Society (2016) Cancer Facts and Figures 2016.

Sadreddini, S., Baradaran, B., Aghebati‐Maleki, A., Sadreddini, S., Shanehbandi, D., Fotouhi, A., Aghebati‐Maleki, L. (2019): Immune checkpoint blockade opens a new way to cancer immunotherapy. Journal of Cellular Physiology 234(6): 8541-8549.

Zhou, X., Hong, T., Yu, Q., Nie, S., Gong, D., Xiong, T., Xie, M. (2017) Exopolysaccharides from Lactobacillus plantarum NCU116 induce c-Jun dependent Fas/Fasl-mediated apoptosis via TLR2 in mouse intestinal epithelial cancer cells. Scientific Reports 7(1): 1-13.

Evivie, S. E., Huo, G. C., Igene, J. O., Bian, X. (2017): Some current applications, limitations and future perspectives of lactic acid bacteria as probiotics. Food & Nutrition Research 61(1): 1318034.

Rad, A. H., Maleki, L. A., Kafil, H. S., Abbasi, A. (2020): Molecular mechanisms of postbiotics in colorectal cancer prevention and treatment. Critical Reviews in Food Science and Nutrition 61(11): 1787-1803.

Berstad, A., Raa, J., Midtvedt, T., Valeur, J. (2016): Probiotic lactic acid bacteria–the fledgling cuckoos of the gut?. Microbial Ecology in Health and Disease 27: 31557.

Arian, S., Kaboosi, H., Heshmatipour, Z., Koohpar, Z. K., Pyravii-Ghadikolaii, F. (2019): Anti-proliferative effects of two new Lactobacillus strains of human origin on Caco-2 cell line. Iranian Red Crescent Medical Journal 21(3): e84683.

Liu, C. F., Pan, T. M. (2010): In vitro effects of lactic acid bacteria on cancer cell viability and antioxidant activity. Journal of Food and Drug Analysis 18(2): 77-86.

Raman, M., Ambalam, P., Kondepudi, K. K., Pithva, S., Kothari, C., Patel, A. T., Purama, R. K., Dave, J. M., Vyas, B. R. M. (2013): Potential of probiotics, prebiotics and synbiotics for management of colorectal cancer. Gut Microbes 4(3): 181-192.

Drago, L. (2019): Probiotics and colon cancer. Microorganisms 7(3): 66.

Narayan, S., Roy, D. (2003): Role of APC and DNA mismatch repair genes in the development of colorectal cancers. Molecular Cancer 2(41): 1-15.

Ambalam, P., Raman, M., Purama, R. K., Doble, M. (2016): Probiotics, prebiotics and colorectal cancer prevention. Best Practice & Research Clinical Gastroenterology 30(1): 119-131.

Kumar, M., Kumar, A., Nagpal, R., Mohania, D., Behare, P., Verma, V., Kumar, P., Poddar, D., Aggarwal, P. K., Henry, C. J. K., Jain, S., Yadav, H. (2010): Cancer-preventing attributes of probiotics: an update. International Journal of Food Sciences and Nutrition 61(5): 473-496.

Orrhage, K., Sillerström, E., Gustafsson, J. Å., Nord, C. E., Rafter, J. (1994): Binding of mutagenic heterocyclic amines by intestinal and lactic acid bacteria. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 311(2): 239-248.

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 Surgery 12(1): 1-8.

Gonzalez, H., Hagerling, C., Werb, Z. (2018): Roles of the immune system in cancer: from tumor initiation to metastatic progression. Genes & Development 32(19-20): 1267-1284.

Chiba, Y., Shida, K., Nagata, S., Wada, M., Bian, L., Wang, C., Shimizu, T., Yamashiro, Y., Kiyoshima-Shibata, J., Nanno, M., Nomoto, K. (2010): Well‐controlled-proinflammatory cytokine responses of Peyer’s patch cells to probiotic Lactobacillus casei. Immunology 130(3): 352-362.

Galdeano, C. M., Perdigon, G. (2006): The probiotic bacterium Lactobacillus casei induces activation of the gut mucosal immune system through innate immunity. Clinical and Vaccine Immunology 13(2): 219-226.

de Roock, S., van Elk, M., van Dijk, M. E. A., Timmerman, H. M., Rijkers, G. T., Prakken, B. J., Hoekstra, M. O., de Kleer, I. M. (2010): Lactic acid bacteria differ in their ability to induce functional regulatory T cells in humans. Clinical & Experimental Allergy 40(1): 103-110.

Donkor, O. N., Ravikumar, M., Proudfoot, O., Day, S. L., Apostolopoulos, V., Paukovics, G., Vasiljevic, T., Nutt, S. L., Gill, H. (2012): Cytokine profile and induction of T helper type 17 and regulatory T cells by human peripheral mononuclear cells after microbial exposure. Clinical & Experimental Immunology 167(2): 282-295.

Smits, H. H., Engering, A., van der Kleij, D., de Jong, E. C., Schipper, K., van Capel, T. M. M., Zaat, B. A. J., Yazdanbakhsh, M., Wierenga, E. A., van Kooyk, Y., Kapsenberg, M. L. (2005): Selective probiotic bacteria induce IL-10–producing regulatory T cells in vitro by modulating dendritic cell function through dendritic cell–specific intercellular adhesion molecule 3–grabbing nonintegrin. Journal of Allergy and Clinical Immunology 115(6): 1260-1267.

Pessione, E. (2012): Lactic acid bacteria contribution to gut microbiota complexity: lights and shadows. Frontiers in Cellular and Infection Microbiology 2(86).

Ren, D. Y., Li, C., Qin, Y. Q., Yin, R. L., Du, S. W., Ye, F., Liu, H. F., Wang, M. P., Sun, Y., Li, X., Tian, M. Y., Jin, N. Y. (2013): Lactobacilli reduce chemokine IL-8 production in response to TNF-α and Salmonella challenge of Caco-2 cells. BioMed Research International, 2013:925219.

Sharma, M., Shukla, G. (2016): Metabiotics: one step ahead of probiotics; an insight into mechanisms involved in anticancerous effect in colorectal cancer. Frontiers in Microbiology 7: 1940.

Wegh, C. A. M., Geerlings, S. Y., Knol, J., Roeselers, G., Belzer, C. (2019): Postbiotics and their potential applications in early life nutrition and beyond. International Journal of Molecular Sciences 20(19): 4673.

Aguilar-Toalá, J. E., Garcia-Varela, R., Garcia, H. S., Mata-Haro, V., González-Córdova, A.F., Vallejo-Cordoba, B., Hernández-Mendoza, A. (2018): Postbiotics: An evolving term within the functional foods field. Trends in Food Science & Technology 75: 105-114.

Nataraj, B. H., Ali, S. A., Behare, P. V., Yadav, H. (2020): Postbiotics-parabiotics: the new horizons in microbial biotherapy and functional foods. Microbial Cell Factories 19(1): 1-22.

Leemhuis, H., Pijning, T., Dobruchowska, J. M., van Leeuwen, S. S., Kralj, S., Dijkstra, B. W., Dijkhuizen, L. (2013): Glucansucrases: three-dimensional structures, reactions, mechanism, α-glucan analysis and their implications in biotechnology and food applications. Journal of Biotechnology 163(2): 250-272.

van Hijum, S. A. F. T., Kralj, S., Ozimek, L. K., Dijkhuizen, L., van Geel-Schutten, I. G. H. (2006): Structure-function relationships of glucansucrase and fructansucrase enzymes from lactic acid bacteria. Microbiology and Molecular Biology Reviews 70(1): 157-176.

Zannini, E., Waters, D. M., Coffey, A., Arendt, E. K. (2016): Production, properties, and industrial food application of lactic acid bacteria-derived exopolysaccharides. Applied Microbiology and Biotechnology 100(3): 1121-1135.

Harutoshi, T. (2013): Exopolysaccharides of lactic acid bacteria for food and colon health applications. In: Kongo, J. M. (ed.) Lactic Acid Bacteria-R&D for Food, Health and Livestock Purposes, InTechOpen, United Kingdom, pp. 515-537.

Sanalibaba, P., Cakmak, G. A. (2016): Exopolysaccharides production by lactic acid bacteria. Applied Microbiology: Open Access 2(2): 1-5.

Sirin, S, Aslim, B. (2020): Characterization of lactic acid bacteria derived exopolysaccharides for use as a defined neuroprotective agent against amyloid beta 1–42-induced apoptosis in SH-SY5Y cells. Scientific Reports 10(1): 8124.

Sirin, S., Aslim, B. (2021): Protective effect of exopolysaccharides from lactic acid bacteria against amyloid beta1-42induced oxidative stress in SH-SY5Y cells: Involvement of the AKT, MAPK, and NF-κB signaling pathway. Process Biochemistry 106: 50-59.

Zheng, J., Wittouck, S., Salvetti, E., Franz, C. M. A. P., Harris, H. M. B., Mattarelli, P., O'Toole, P. W., Pot, B., Vandamme, P., Walter, J., Watanabe, K., Wuyts, S., Felis, G. E., Gänzle, M. G., Lebeer, S. (2020): A taxonomic note on the genus Lactobacillus: Description of 23 novel genera, emended description of the genus Lactobacillus Beijerinck 1901, and union of Lactobacillaceae and Leuconostocaceae. International Journal of Systematic and Evolutionary Microbiology 70(4): 2782-2858.

Tsuda, H., Hara, K., Miyamoto, T. (2008): Binding of mutagens to exopolysaccharide produced by Lactobacillus plantarum mutant strain 301102S. Journal of Dairy Science 91(8): 2960-2966.

Dubois, M., Gilles, K. A., Hamilton, J. K., Rebers, P. A., Smith, F. (1956): Colorimetric method for determination of sugars and related substances. Analytical Chemistry 28(3): 350-356.

Nielsen, S. S. (2010): Phenol-sulfuric acid method for total carbohydrates. In: Nielsen, S. S. (ed.) Food Analysis Laboratory Manual, Springer, Boston, USA, pp. 47-53.

Wang, B., Li, J., Chen, J., Huang, Q., Li, N., Li, J. (2010): Effect of live Lactobacillus plantarum L2 on TNF-α-induced MCP-1 production in Caco-2 cells. International journal of food microbiology 142(1-2): 237-241.

Wu, S. C., Wang, F. J., Pan, C. L. (2007): Growth and survival of lactic acid bacteria during the fermentation and storage of seaweed oligosaccharides solution. Journal of Marine Science and Technology 15(2): 104-114.

You, H. J., Oh, D.K., Ji, G. E. (2004): Anticancerogenic effect of a novel chiroinositol-containing polysaccharide from Bifidobacterium bifidum BGN4. FEMS Microbiology Letters 240(2): 131-136.

Hong, H. A., Huang, J. M., Khaneja, R., Hiep, L. V., Urdaci, M. C., Cutting, S. M. (2008): The safety of Bacillus subtilis and Bacillus indicus as food probiotics. Journal of Applied Microbiology 105(2): 510-520.

Liu, C. T., Chu, F. J., Chou, C. C., Yu, R. C. (2011): Antiproliferative and anticytotoxic effects of cell fractions and exopolysaccharides from Lactobacillus casei 01. Mutation Research/Genetic Toxicology and Environmental Mutagenesis 721(2): 157-162.

Mosaffa, F., Behravan, J., Karimi, G., Iranshahi, M. (2006): Antigenotoxic effects of Satureja hortensis L. on rat lymphocytes exposed to oxidative stress. Archives of Pharmacal Research 29(2): 159-164.

Park, E., Jeon, K. I., Byun, B. H. (2005): Ethanol extract of Inonotus obliquus shows antigenotoxic effect on hydrogen peroxide induced DNA damage in human lymphocytes. Cancer Prevention Research 10(1): 54-59.

Singh, N. P., McCoy, M. T., Tice, R. R., Schneider, E. L. (1988): A simple technique for quantitation of low levels of DNA damage in individual cells. Experimental Cell Research 175(1): 184-191.

Noroozi S, Mosaffa F, Soltani F., Iranshahi, M., Karimi, G., Malekaneh, M., Haghighi, F., Behravan, J. (2009): Antigenotoxic effects of the disulfide compound persicasulfide A (PSA) on rat lymphocytes exposed to oxidative stress. Planta Medica 75(1): 32-36.

Raipulis, J., Toma, M. M., Semjonovs, P. (2005): The effect of probiotics on the genotoxicity of furazolidone. International Journal of Food Microbiology 102(3): 343-347.

Bai, A. P., Ouyang, Q., Zhang, W., Wang, C. H., Li, S. F. (2004): Probiotics inhibit TNF-α-induced interleukin-8 secretion of HT29 cells. World Journal of Gastroenterology 10(3): 455-457.

Gao, Q., Qi, L., Wu, T., Wang, J. (2012): An important role of interleukin-10 in counteracting excessive immune response in HT-29 cells exposed to Clostridium butyricum. BMC Microbiology 12(1): 1-8.

Jijon, H., Backer, J., Diaz, H., Yeung, H., Thiel, D., McKaigney, C., de Simone, C., Madsen, K. (2004): DNA from probiotic bacteria modulates murine and human epithelial and immune function. Gastroenterology 126(5): 1358-1373.

Kim, H., Jung, B. J., Jung, J. H., Kim, J. Y., Chung, S. K., Chung, D. K. (2012): Lactobacillus plantarum lipoteichoic acid alleviates TNF-α-induced inflammation in the HT-29 intestinal epithelial cell line. Molecules and Cells 33(5): 479-486.

Vemuri, R., Shinde, T., Shastri, M. D., Perera, A. P., Tristram, S., Martoni, C. J., Gundamaraju, R., Ahuja, K. D. K., Ball, M., Eri, R. (2018): A human origin strain Lactobacillus acidophilus DDS-1 exhibits superior in vitro probiotic efficacy in comparison to plant or dairy origin probiotics. International Journal of Medical Sciences 15(9): 840–848.

van de Wiele, T., Boon, N., Possemiers, S., Jacobs, H., Verstraete, W. (2004): Prebiotic effects of chicory inulin in the simulator of the human intestinal microbial ecosystem. FEMS Microbiology Ecology 51(1): 143-153.

Angelin, J., Kavitha, M. (2020): Exopolysaccharides from probiotic bacteria and their health potential. International Journal of Biological Macromolecules 162: 853–865.

Kitazawa, H., Harata, T., Uemura, J., Saito, T., Kaneko, T., Itoh, T. (1998): Phosphate group requirement for mitogenic activation of lymphocytes by an extracellular phosphopolysaccharide from Lactobacillus delbrueckii ssp. bulgaricus. International Journal of Food Microbiology 40(3): 169-175.

Dupont, I., Roy, D., Lapointe, G. (2000): Comparison of exopolysaccharide production by strains of Lactobacillus rhamnosus and Lactobacillus paracasei grown in chemically defined medium and milk. Journal of Industrial Microbiology and Biotechnology 24(4): 251-255.

Mende, S., Krzyzanowski, L., Weber, J., Jaros, D., Rohm, H. (2012): Growth and exopolysaccharide yield of Lactobacillus delbrueckii ssp. bulgaricus DSM 20081 in batch and continuous bioreactor experiments at constant pH. Journal of Bioscience and Bioengineering 113(2): 185-191.

Huang, Y., Adams, M. C. (2003): An in vitro model for investigating intestinal adhesion of potential dairy propionibacteria probiotic strains using cell line C2BBe1. Letters in Applied Microbiology 36(4): 213-216.

Chuah, L. O., Foo, H. L., Loh, T. C., Alitheen, N. B. M., Yeap, S. K., Mutalib, N. E. A., Rahim, R. A., Yusoff, K. (2019): Postbiotic metabolites produced by Lactobacillus plantarum strains exert selective cytotoxicity effects on cancer cells. BMC Complementary and Alternative Medicine 19(1): 1-12.

Grimoud, J., Durand, H., de Souza, S., Monsan, P., Ouarné, F., Theodorou, V., Roques, C. (2010): In vitro screening of probiotics and synbiotics according to anti-inflammatory and anti-proliferative effects. International Journal of Food Microbiology 144(1): 42-50.

Tuo, Y. F., Zhang, L. W., Yi, H. X., Zhang, Y. C., Zhang, W. Q., Han, X., Du, M., Jiao, Y. H., Wang, S. M. (2010): Antiproliferative effect of wild Lactobacillus strains isolated from fermented foods on HT-29 cells. Journal of Dairy Science 93(6): 2362-2366.

Piqué, N., Berlanga, M., Miñana-Galbis, D. (2019): Health benefits of heat-killed (Tyndallized) probiotics: an overview. International Journal of Molecular Sciences 20(10): 2534.

Rad, A. H., Maleki, L. A., Kafil, H. S., Zavoshti, H. F., Abbasi, A. ( 2020): Postbiotics as novel health-promoting ingredients in functional foods. Health Promot Perspect 10(1): 3-4.

Pedraza-Fariña, L. G. (2006): Cancer issue: mechanisms of oncogenic cooperation in cancer initiation and metastasis. The Yale Journal of Biology and Medicine 79(3-4): 95-103.

Wollowski, I., Ji, S. T., Bakalinsky, A. T., Neudecker, C., Pool-Zobel, B. L. (1999): Bacteria used for the production of yogurt inactivate carcinogens and prevent DNA damage in the colon of rats. The Journal of Nutrition 129(1): 77-82.

Li, W., Li, C. B. (2003): Lack of inhibitory effects of lactic acid bacteria on 1, 2-dimethylhydrazine-induced colon tumors in rats. World Journal of Gastroenterology 9(11): 2469-2473.

Koller, V. J., Marian, B., Stidl, R., Nersesyan, A., Winter, H., Simić, T., Sontag, G., Knasmüller, S. (2008): Impact of lactic acid bacteria on oxidative DNA damage in human derived colon cells. Food and Chemical Toxicology 46(4): 1221-1229.

Qazi, B. S., Tang, K., Qazi, A. (2011): Recent advances in underlying pathologies provide insight into interleukin-8 expression-mediated inflammation and angiogenesis. International Journal of Inflammation 2011: 908468.

Huang, J., Wang, M. D., Lenz, S., Gao, D., Kaltenboeck, B. (1999): IL-12 administered during Chlamydia psittaci lung infection in mice confers immediate and long-term protection and reduces macrophage inflammatory protein-2 level and neutrophil infiltration in lung tissue. The Journal of Immunology 162(4): 2217-2226.

Sato, T., Terai, M., Tamura, Y., Alexeev, V., Mastrangelo, M. J., Selvan, S. R. (2011): Interleukin 10 in the tumor microenvironment: a target for anticancer immunotherapy. Immunologic Research 51(2): 170-182.

Fujiki, T., Hirose, Y., Yamamoto, Y., Murosaki, S. (2012): Enhanced immunomodulatory activity and stability in simulated digestive juices of Lactobacillus plantarum L-137 by heat treatment. Bioscience, Biotechnology, and Biochemistry 76(5): 918-922.

Miyazawa, K., He, F., Kawase, M., Kubota, A., Yoda, K., Hiramatsu, M. (2011): Enhancement of immunoregulatory effects of Lactobacillus gasseri TMC0356 by heat treatment and culture medium. Letters in Applied Microbiology 53(2): 210-216.

de Moreno de LeBlanc, A., del Carmen, S., Zurita-Turk, M., Santos Rocha, C., van de Guchte, M., Azevedo, V., Miyoshi, A., LeBlanc, J. G. (2011): Importance of IL-10 modulation by probiotic microorganisms in gastrointestinal inflammatory diseases. ISRN Gastroenterology 2011: 892971.




How to Cite

Nigdelioglu Dolanbay, S., & Aslim, B. (2022). COMPARISON OF THE ANTI-CARCINOGENIC EFFECTS OF SOME PROBIOTIC BACTERIA AND THEIR POSTBIOTICS ON COLORECTAL CANCER CELLS. Journal of Applied Biological Sciences, 16(2), 308–325. Retrieved from