Emre EVİN, Orhan ADALI, Yavuz ERDEN, Busenur ÇELEBİ, Hasan Ufuk CELEBIOGLU

Cytotoxic Effects of Probiotic Bacteria Lactobacillus acidophilus and Lactobacillus rhamnosus Grown in the Presence of Oleuropein on Human Prostate Cancer Cells

Functional foods are groups of foods that have potentially positive effects on health beyond basicnutrition. Probiotics are beneficial microorganisms, being as a group of functional foods, and wheningested in adequate amounts, they possess positive health effects to host organisms including havinganti-carcinogenic functions, yet their exact mechanisms how they possess anti-carcinogenic activitiesare still under investigation. Another group of functional foods is plant-based phenolic compounds.They also have potential to possess anti-carcinogenic activities. Among them, oleuropein is veryinteresting and well-known phenolic compound naturally present in olive fruits and olive oil. As thephenolic compounds and probiotic bacteria can be present at the same time in human gastrointestinaltract, this study aims to investigate the in vitro cytotoxic effects of Lactobacillus acidophilus LA-5 (LA5) and Lactobacillus rhamnosus GG (GG) grown in the presence of oleuropein on human prostatecancer cell line. For this, oleuropein was added to media of these bacteria and effects of cell-freesupernatants of these combinations (phenolic+probiotic) on cytotoxicity of prostate cancer cell line PC-3were investigated using MTT Method. Different concentrations of oleuropein were added to bacterialcultures and oleuropein added to the growth medium of LA-5 had additional effects on the cytotoxicityof cell-free supernatants of this bacterium. However, addition of oleuropein to the growth medium ofGG did not show significant changes on the cytotoxicity of cell-free supernatants of this bacterium.Thus, the results indicate that new combinations of functional foods have potential to formulate newnutraceuticals.

PDF

___

1. Roberfroid MB. 2000. A European Consensus of Scientific Concepts of Functional Foods, Nutrition, 16 (7-8): 689-144.
2. Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, Morelli L, Canani RB, Flint HJ, Salminen S, Calder PC, Sanders ME. 2014. Expert Consensus Document: The International Scientific Association for Probiotics and Prebiotics Consensus Statement on the Scope and Appropriate Use of the Term Probiotic, Nature Reviews Gastroenterology and Hepatology, 11 (Augst 2014): 9.
3. Uymaz B. 2010. Probiyotikler ve Kullanım Alanları, Pamukkale Üniversitesi, Mühendislik Bilim Dergisi, 16 (1): 2010, 95-104.
4. Gülgör G, Özçelik F. 2014. Bakteriyosin Üreten Laktik Asit Bakterilerinin Probiyotik Amaçlı Kullanımı, Akademik Gıda, 12 (1): 63-68.
5. Servin AL, Coconnier MH. 2003. Adhesion of Probiotic Strains to the Intestinal Mucosa and İnteraction with Pathogens, Best Practice Research Clinical Gastroenterology, 17 (5): 741-754.
6. Celebioglu HU, Svensson B. 2018. Dietary Nutrients, Proteomes, and Adhesion of Probiotic Lactobacilli to Mucin and Host Epithelial Cells, Microorganisms, 6 (3): 90.
7. Wichers HJ, Soler-Rivas C, Espin JC. 2000. Oleuropein and Related Compounds, Journal of the Science of Food and Agriculture, 80 (7): 1013-1023.
8. Servili M, Baldioli M, Selvaggini R, Macchioni A, Montedoro GF. 1999. Phenolic Compounds of Olive Fruit: One- and TwoDimensional Nuclear Magnetic Resonance Characterization of Nuzhenide and its Distribution in the Constitutive Parts of Fruit, Journal of Agricultural and Food Chemistry, 47 (1): 12-18.
9. Omar SH. 2010. Oleuropein in Olive and its Pharmacological Effects, Scientia Pharmaceutica, 78 (2): 133-154.
10. Visioli F, Galli C, Galli G, Caruso D. 2002. Biological Activities and Metabolic Fate of Olive Oil Phenols, European Journal of Lipid Science and Technology, 104 (9-10): 677-684.
11. De la Puerta R, Domínguez MEM, Ruíz-Gutíerrez V, Flavill JA, Hoult JRS. 2001. Effects of Virgin Olive Oil Phenolics on Scavenging of Reactive Nitrogen Species and Upon Nitrergic Neurotransmission. Life Sciences, 69 (10): 1213-1222.
12. Saija A, Trombetta D, Tomaino A, Lo Cascio R, Princi P, Uccella N, Bonina F, Castelli F. 1998. In-vitro Evaluation of the Antioxidant Activity and Biomembrane Interaction of the Plant Phenols Oleuropein and Hydroxytyrosol, International Journal of Pharmaceutics, 166: 123-133.
13. Bisignano G, Tomaino A, Lo Cascio R, Crisafi G, Uccella N, Saija A. 1999. On the In-vitro Antimicrobial Activity of Oleuropein and Hydroxytyrosol, Journal of Pharmacy and Pharmacology, 51 (8): 971-4.
14. Fleming HP, Walter WM, Etchells JL. 1973. Antimicrobial Properties of Oleuropein and Products of its Hydrolysis From Green Olives, Journal of Applied Microbiology, 26 (5): 777-782.
15. Furneri PM, Marino A, Saija A, Uccella N, Bisignano G. 2002. In vitro Antimycoplasmal Activity of Oleuropein, International Journal of Antimicrobial Agents, 20 (4): 293-6.
16. Hamdi HK., Castellon R. 2005. Oleuropein, a Non-Toxic Olive Iridoid, is an Anti-Tumor Agent and Cytoskeleton Disruptor, Biochemical and Biophysical Research Communications, 334 (3): 769-78.
17. Menendez JA, Colomer R, Carrasco-Pancorbo A, FernándezGutiérrez A, Vazquez-Martin A, Brunet J, Villalba RG, Carretero AS. 2007. Olive Oil’s Bitter Principle Reverses Acquired Autoresistance to Trastuzumab (HerceptinTM) in HER2- Overexpressing Breast Cancer Cells, BMC Cancer, 7 (1): 80.
18. Celebioglu HU, Delsoglio M, Brix S, Pessione E, Svensson B. 2018. Plant Polyphenols Stimulate Adhesion to Intestinal Mucosa and Induce Proteome Changes in the Probiotic Lactobacillus acidophilus NCFM, Molecular Nutrition & Food Research, 62 (4): 1-11.
19. Denizot F., Lang R.1986. Rapid Colorimetric Assay for Cell Growth and Survival. Modifications to the Tetrazolium Dye Procedure Giving Improved Sensitivity and Reliability, Journal of Immunological Methods, 89 (2): 271-7.
20. Thirabunyanon M, Boonprasom P, Niamsup P. 2009. Probiotic Potential of Lactic Acid Bacteria Isolated from Fermented Dairy Milks on Antiproliferation of Colon Cancer Cells, Biotechnology Letters, 31 (4): 571-6.
21. Celebioglu HU, Celebi B.. Zeytinyağı Fenoliklerinden Oleuropeinin Probiyotik Lactobacillus acidophilus ve Lactobacillus rhamnosus Bakterileri Üzerine Etkileri, Uluslararası Marmara Fen ve Sosyal Bilimler Kongresi, Fen Bilimleri Bildiriler Kitabı Cilt I, Kocaeli-Turkey, 2019, pp 429- 436.
22. Krasowska A., Sigler K. 2014. How Microorganisms Use Hydrophobicity and What Does this Mean for Human Needs?, Frontiers in Cellular and Infection Microbiology, 4: 112.
23. Juge N. 2012. Microbial Adhesins to Gastrointestinal Mucus, Trends in Microbiology, 20 (1): 30-9.
24. Collado MC, Meriluoto J, Salminen S. 2007. Adhesion and Aggregation Properties of Probiotic and Pathogen Strains, European Food Research and Technology, 226 (5): 1065-1073.
25. An YH, Friedman RJ, An YH., Dickinson RB, Doyle RJ 2003. Mechanisms of Bacterial Adhesion and Pathogenesis of Implant and Tissue Infections. In: An YH and Friedman RJ Handbook of Bacterial Adhesion, Humana Press, Totowa, NJ, pp 1-27.
26. Ouwehand AC, Salminen S. 2003. In vitro Adhesion Assays for Probiotics and their İn vivo Relevance: a Review, Microbial Ecology in Health and Disease, 15 (4): 175-184.
27. Ferlay J., Steliarova-Foucher E., Lortet-Tieulent J., Rosso S., Coebergh J. W. W., Comber H., Forman D., Bray F. 2015. Reprint of: Cancer Incidence and Mortality Patterns in Europe: Estimates for 40 Countries in 2012, European Journal of Cancer, 51 (9): 1201-1202.
28. Siegel R., Ma J., Zou Z., Jemal A. 2014. Cancer Statistics, 2014, CA: A Cancer Journal for Clinicians, 64 (1): 9-29.
29. Cimino S, Sortino G., Favilla V., Castelli T., Madonia M., Sansalone S., Russo G., Morgio G. 2012. Polyphenols: Key Issues Involved in Chemoprevention of Prostate Cancer, Oxidative Medicine and Cellular Longevity, 2012: 632959.
30. Imran M., Nadeem M., Gilani S. A., Khan S., Sajid M. W., Amir R. M. 2018. Antitumor Perspectives of Oleuropein and Its Metabolite Hydroxytyrosol: Recent Updates, Journal of Food Science, 83 (7): 1781-1791.
31. Luo C., Li Y., Wang H., Cui Y., Feng Z., Li H., Li Y., Wang Y., Wurtz K., Weber P., Long J., Liu J. 2013. Hydroxytyrosol Promotes Superoxide Production and Defects in Autophagy Leading to Anti-proliferation and Apoptosis on Human Prostate Cancer Cells, Current Cancer Drug Targets, 13 (6): 625-39.
32. Zubair H., Bhardwaj A ., Ahmad A., Srivastava SK ., Khan M.A ., Patel GK ., Singh S . 2017. Hydroxytyrosol Induces Apoptosis and Cell Cycle Arrest and Suppresses Multiple Oncogenic Signaling Pathways in Prostate Cancer Cells, Nutrition and Cancer, 69 (6): 932-942.
33. Atmaca H., Çamlı Ç., Sert S. 2018. Ethanol Extract of Pinus nigra ssp. pallasiana var. şeneriana Inhibits Human Breast Cancer Cell Viability through Induction of Apoptosis, Celal Bayar University Journal of Science, 14 (1):35-40.
34. Atmaca H. 2017. Effects of Galium aparine Extract on the Angiogenic Cytokines and ERK1/2 Proteins in Human Breast Cancer Cells, Celal Bayar University Journal of Science, 13 (1):171-179.
35. Karakurt S., Adali O. 2016. Tannic Acid Inhibits Proliferation, Migration, Invasion of Prostate Cancer and Modulates Drug Metabolizing and Antioxidant Enzymes, Anti-Cancer Agents in Medicinal Chemistry, 16 (6):781-789.