Abstract
Saccharomyces cerevisiae var. boulardii has been used as a probiotic yeast in the medical and food industries. Colon cancers have been known as the third most common cancer type worldwide. Nowadays, cell-free extract and metabolites of probiotics have been employed for the treatment or prevention of different cancer diseases. This study investigates the anticancer properties of S. boulardii metabolites against human colon carcinoma. We evaluated cytotoxicity, apoptosis induction, and suppression of survivin, IL-8, and NFƙB gene expression effects of SBM against caco-2 cells after 24 and 48 h. IC50 concentrations of SBM were measured at 815 and 1411 µg/mL for 24 and 48 h treatments, respectively. The total proportion of apoptotic caco-2 cells treated with SBM after 24 and 48 h were calculated at 62.23 and 88.7%, respectively. Also, relative expression of survivin, IL-8, and NFƙB genes were significantly suppressed in caco-2 cells treated with SBM after 24 and 48 h. In conclusion, we found that SBM induced apoptosis, inhibited the growth rate, and suppressed the expression of the survivin, IL-8, and NFƙB genes in human colorectal cancer cells and it can be considered as a perspective supplement or drug for the treatment or prevention of colon cancer in humans.
Similar content being viewed by others
Data Availability
We confirm that all the data and findings of this study are available within the article.
Code Availability
Not applicable.
References
Ahmed M (2020) Colon cancer: a clinician’s perspective in 2019. Gastroenterology Res 13:1
Rafiemanesh H, Pakzad R, Abedi M et al (2016) Colorectal cancer in Iran: epidemiology and morphology trends. EXCLI J 15:738
Chakrabarti S, Peterson CY, Sriram D et al (2020) Early stage colon cancer: current treatment standards, evolving paradigms, and future directions. World J Gastrointest Oncol 12:808
Fotheringham S, Mozolowski GA, Murray EM et al (2019) Challenges and solutions in patient treatment strategies for stage II colon cancer. Gastroenterology report 7:151–161
Plaza-Diaz J, Ruiz-Ojeda FJ, Gil-Campos M et al (2019) Mechanisms of action of probiotics. Adv Nutr 10:S49–S66
Sanders M, Merenstein D, Merrifield C et al (2018) Probiotics for human use Nutrition bulletin 43:212–225
Stavropoulou E, Bezirtzoglou E (2020) Probiotics in medicine: a long debate. Front Immunol 11:2192
Trush EA, Poluektova EA, Beniashvilli AG et al (2020) The evolution of human probiotics: challenges and prospects. Probiotics and antimicrobial proteins 12:1291–1299
Wan MLY, Forsythe SJ, El-Nezami H (2019) Probiotics interaction with foodborne pathogens: a potential alternative to antibiotics and future challenges. Crit Rev Food Sci Nutr 59:3320–3333
Żółkiewicz J, Marzec A, Ruszczyński M et al (2020) Postbiotics—a step beyond pre-and probiotics. Nutrients 12:2189
Shenderov BA, Sinitsa AV, Zakharchenko M et al (2020) Metabiotics. Springer
Shenderov BA, Sinitsa AV, Zakharchenko MM et al (2020) Cellular metabiotics and metabolite metabiotics. In: Metabiotics. Springer, p 63–75
Singh A, Vishwakarma V, Singhal B (2018) Metabiotics: the functional metabolic signatures of probiotics: current state-of-art and future research priorities—metabiotics: probiotics effector molecules. Adv Biosci Biotechnol 9:147
Pais P, Almeida V, Yılmaz M et al (2020) Saccharomyces boulardii: what makes it tick as successful probiotic? J Fungi 6:78
Imre A, Kovács R, Pázmándi K et al (2021) Virulence factors and in-host selection on phenotypes in infectious probiotic yeast isolates (Saccharomyces ‘boulardii’). J Fungi 7:746
Pakbin B, Dibazar SP, Allahyari S et al (2022) Anticancer properties of probiotic Saccharomyces boulardii supernatant on human breast cancer cells. Probiotics Antimicrob 1–9
Allahyari S, Dibazar SP, Pakbin B et al (2020) Anticancer effect of probiotic Saccharomyces boulardii supernatant on human caco-2 cells: an in vitro study. Carpathian J Food Sci Technol 12
Ashrafi Tamai I, Mohammadzadeh A, Zahraei Salehi T et al (2021) Investigation of antimicrobial susceptibility and virulence factor genes in Trueperella pyogenes isolated from clinical mastitis cases of dairy cows. Food Sci Nutr 9:4529–4538
Fu J, Liu J, Wen X et al (2022) Unique probiotic properties and bioactive metabolites of Saccharomyces boulardii. Probiotics Antimicrob 1–16
An Z, Li J, Yu J et al (2019) Neutrophil extracellular traps induced by IL-8 aggravate atherosclerosis via activation NF-κB signaling in macrophages. Cell Cycle 18:2928–2938
Rao X, Huang X, Zhou Z et al (2013) An improvement of the 2ˆ (–delta delta CT) method for quantitative real-time polymerase chain reaction data analysis. Biostatistics, bioinformatics and biomathematics 3:71
Azevedo L, Chagas-Paula DA, Kim H et al (2016) White mold (Sclerotinia sclerotiorum), friend or foe: cytotoxic and mutagenic activities in vitro and in vivo. Food Res Int 80:27–35
Geng R, Tan X, Wu J et al (2017) RNF183 promotes proliferation and metastasis of colorectal cancer cells via activation of NF-κB-IL-8 axis. Cell Death Dis 8:e2994–e2994
Zein R, Alghoraibi I, Soukkarieh C et al (2020) In-vitro anticancer activity against Caco-2 cell line of colloidal nano silver synthesized using aqueous extract of Eucalyptus camaldulensis leaves. Heliyon 6:e04594
Fan X, Guo H, Teng C et al (2022) Anti-colon cancer activity of novel peptides isolated from in vitro digestion of quinoa protein in caco-2 cells. Foods 11:194
Awadelkareem AM, Al-Shammari E, Elkhalifa AEO et al (2022) Phytochemical and in silico ADME/Tox analysis of Eruca sativa extract with antioxidant, antibacterial and anticancer potential against Caco-2 and HCT-116 colorectal carcinoma cell lines. Molecules 27:1409
Nozari S, Faridvand Y, Etesami A et al (2019) Potential anticancer effects of cell wall protein fractions from Lactobacillus paracasei on human intestinal Caco-2 cell line. Lett Appl Microbiol 69:148–154
Nowak A, Zakłos-Szyda M, Rosicka-Kaczmarek J et al (2022) Anticancer potential of post-fermentation media and cell extracts of probiotic strains: an in vitro study. Cancers 14:1853
Adiyoga R, Arief II, Budiman C et al (2022) In vitro anticancer potentials of Lactobacillus plantarum IIA-1A5 and Lactobacillus acidophilus IIA-2B4 extracts against WiDr human colon cancer cell line. Food Sci Technol 42
Datta S, Timson DJ, Annapure US (2017) Antioxidant properties and global metabolite screening of the probiotic yeast Saccharomyces cerevisiae var. boulardii. J Sci Food Agric 97:3039–3049
Vahed SZ, Barzegari A, Saadat YR et al (2017) Leuconostoc mesenteroides-derived anticancer pharmaceuticals hinder inflammation and cell survival in colon cancer cells by modulating NF-κB/AKT/PTEN/MAPK pathways. Biomed Pharmacother 94:1094–1100
Sharma M, Chandel D, Shukla G (2020) Antigenotoxicity and cytotoxic potentials of metabiotics extracted from isolated probiotic, Lactobacillus rhamnosus MD 14 on Caco-2 and HT-29 human colon cancer cells. Nutr Cancer 72:110–119
Sharma M, Shukla G (2020) Administration of metabiotics extracted from probiotic Lactobacillus rhamnosus MD 14 inhibit experimental colorectal carcinogenesis by targeting Wnt/β-catenin pathway. Front Oncol 10:746
Pourbaferani M, Modiri S, Norouzy A et al (2021) A newly characterized potentially probiotic strain, Lactobacillus brevis MK05, and the toxicity effects of its secretory proteins against MCF-7 breast cancer cells. Probiotics Antimicrob 13:982–992
Kim H-J, An J, Ha E-M (2022) Lactobacillus plantarum-derived metabolites sensitize the tumor-suppressive effects of butyrate by regulating the functional expression of SMCT1 in 5-FU-resistant colorectal cancer cells. J Microbiol 60:100–117
Oh T-I, Lee Y-M, Nam T-J et al (2017) Fascaplysin exerts anti-cancer effects through the downregulation of survivin and HIF-1α and inhibition of VEGFR2 and TRKA. Int J Mol Sci 18:2074
Sougioultzis S, Simeonidis S, Bhaskar KR et al (2006) Saccharomyces boulardii produces a soluble anti-inflammatory factor that inhibits NF-κB-mediated IL-8 gene expression. Biochem Biophys Res Commun 343:69–76
Acknowledgements
We appreciate all the technicians and our colleagues at the Medical Microbiology Research Center, Qazvin University of Medical Sciences, who assisted us in this research project.
Author information
Authors and Affiliations
Contributions
Babak Pakbin, Samaneh Allahyari, Shaghayegh Pishkhan Dibazar, and Mozhdeh Khajeh Haghverdi implemented the cellular and molecular experiments, including SBM preparation, cell culture, treatments, MTT assay, and relative gene expression; Amir Peymani, Khadijeh Taherkhani, and Maryam Javadi implemented the flow cytometry analysis; Babak Pakbin analyzed all the results and wrote and reviewed the first draft of the manuscript; Razzagh Mahmoudi supervised and managed the project, provided the sources, and revised the final draft of the manuscript. All the authors read and approved the final manuscript.
Corresponding author
Ethics declarations
Ethics Approval
Not applicable.
Consent to Participate
Not applicable.
Consent for Publication
Not applicable.
Conflict of Interest
The authors declare no competing interests.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Pakbin, B., Allahyari, S., Dibazar, S.P. et al. Anticancer Properties of Saccharomyces boulardii Metabolite Against Colon Cancer Cells. Probiotics & Antimicro. Prot. 16, 224–232 (2024). https://doi.org/10.1007/s12602-022-10030-w
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12602-022-10030-w