Anticancer Activity of Postbiotic Mediators Derived from Lactobacillus Rhamnosus GG and Lactobacillus Reuteri on Acute Lymphoblastic Leukemia Cells
DOI:
https://doi.org/10.31661/gmj.v12i.3096Keywords:
Cancer, Acute Lymphoblastic Leukemia, Probiotic, Postbiotic, AnticancerAbstract
Background: Leukemia remains a global health challenge, requiring the exploration of alternative therapies with reduced side effects. Probiotics, particularly Lactobacillus species, have gained attention because of their potential anticancer properties. This study investigated the anticancer and cytotoxic effects of postbiotic mediators (PMs) derived from Lactobacillus rhamnosus GG (LGG) and Lactobacillus reuteri (LR) on acute lymphoblastic leukemia (ALL) cells and peripheral blood mononuclear cells (PBMCs). Materials and Methods: The PMs were prepared by culturing LGG and LR strains and isolating the supernatant. The MTT assay assessed cell viability on ALL Jurkat cells and PBMCs, and apoptosis analysis was conducted using flow cytometry. Quantitative real-time PCR was also performed to analyze BAX, BCL-2, BCLX, FAS, and p27 gene expression levels. Results: The results showed that PMs derived from LGG and LR significantly reduced cell viability in Jurkat cells (P<0.05) but not PBMCs (P>0.05). Apoptosis analysis revealed an increase in apoptotic cells after PMs treatment. Nevertheless, gene expression analysis revealed no statistically significant difference between the treated and untreated groups in BAX, BCL-2, BCLX, FAS, and p27 gene expression levels (P>0.05). Conclusion: Findings suggest that specific PMs derived from LGG and LR possess anticancer properties against ALL cells. This research highlighted the promise of PMs as a cutting-edge and less toxic adjuvant therapeutic strategy in cancer treatment.
References
Sung H, Ferlay J, Siegel R, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71: 209-49. https://doi.org/10.3322/caac.21660PMid:33538338 Pui C-H, Yang JJ, Hunger SP, Pieters R, Schrappe M, Biondi A, et al. Childhood Acute Lymphoblastic Leukemia: Progress Through Collaboration. J Clin Oncol. 2015;33(27):2938-48. https://doi.org/10.1200/JCO.2014.59.1636PMid:26304874 PMCid:PMC4567699 Wu C, Li W. Genomics and pharmacogenomics of pediatric acute lymphoblastic leukemia. Crit Rev Oncol Hematol. 2018;126:100-11. https://doi.org/10.1016/j.critrevonc.2018.04.002PMid:29759551 Hunger SP, Mullighan CG. Acute Lymphoblastic Leukemia in Children. N Engl J Med. 2015;373(16):1541-52. https://doi.org/10.1056/NEJMra1400972PMid:26465987 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. Galdeano CM, Cazorla SI, Dumit JML, Vélez E, Perdigón G. Beneficial effects of probiotic consumption on the immune system. Ann Nutr Metab. 2019;74(2):115-24. https://doi.org/10.1159/000496426PMid:30673668 Alam Z, Shang X, Effat K, Kanwal F, He X, Li Y, et al. The potential role of prebiotics, probiotics, and synbiotics in adjuvant cancer therapy especially colorectal cancer. J Food Biochem. 2022;46(10):e14302. https://doi.org/10.1111/jfbc.14302PMid:35816322 Ghorbani E, Avan A, Ryzhikov M, Ferns G, Khazaei M, Soleimanpour S. Role of Lactobacillus strains in the management of colorectal cancer An overview of recent advances. Nutrition. 2022:111828. https://doi.org/10.1016/j.nut.2022.111828PMid:36162222 Thomas CM, Hong T, Van Pijkeren JP, Hemarajata P, Trinh DV, Hu W, et al. Histamine derived from probiotic Lactobacillus reuteri suppresses TNF via modulation of PKA and ERK signaling. PLoS One. 2012;7(2):e31951. https://doi.org/10.1371/journal.pone.0031951PMid:22384111 PMCid:PMC3285189 Lozenov S, Krastev B, Nikolaev G, Peshevska-Sekulovska M, Peruhova M, Velikova T. Gut Microbiome Composition and Its Metabolites Are a Key Regulating Factor for Malignant Transformation, Metastasis and Antitumor Immunity. Int J Mol Sci. 2023;24(6):5978. https://doi.org/10.3390/ijms24065978PMid:36983053 PMCid:PMC10054493 Thorakkattu P, Khanashyam AC, Shah K, Babu KS, Mundanat AS, Deliephan A, et al. Postbiotics: Current trends in food and Pharmaceutical industry. Foods. 2022;11(19):3094. https://doi.org/10.3390/foods11193094PMid:36230169 PMCid:PMC9564201 Aguilar-Toalá JE, Garcia-Varela R, Garcia HS, Mata-Haro V, González-Córdova AF, Vallejo-Cordoba B, et al. Postbiotics: An evolving term within the functional foods field. Trends Food Sci Technol. 2018;75:105-14. https://doi.org/10.1016/j.tifs.2018.03.009 Ambesh P, Stroud S, Franzova E, Gotesman J, Sharma K, Wolf L, et al. Recurrent Lactobacillus Bacteremia in a Patient With Leukemia. J Investig Med High Impact Case Rep. 2017;5(4):2324709617744233. https://doi.org/10.1177/2324709617744233PMid:29204452 PMCid:PMC5703097 Zitvogel L, Daillère R, Roberti MP, Routy B, Kroemer G. Anticancer effects of the microbiome and its products. Nat Rev Microbiol. 2017;15(8):465-78. https://doi.org/10.1038/nrmicro.2017.44PMid:28529325 Sharma M, Chandel D, Shukla G. 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. 2020;72(1):110-9. https://doi.org/10.1080/01635581.2019.1615514PMid:31266374 Schaefer L, Auchtunger F, Mallett G, Foerster F, Porter A, Malvezzi M, et al. Global trends in colorectal cancer mortality: projections to the year 2035. Int J Cancer. 2018; 142(12): 2489-96. Zahran WE, Elsonbaty SM, Moawed FSM. Lactobacillus rhamnosus ATCC 7469 exopolysaccharides synergizes with low level ionizing radiation to modulate signaling molecular targets in colorectal carcinogenesis in rats. Biomed Pharmacother. 2017;92:384-93. https://doi.org/10.1016/j.biopha.2017.05.089PMid:28554134 Banakar M, Pourhajibagher M, Etemad-Moghadam S, Mehran M, Yazdi MH, Haghgoo R, et al. Antimicrobial Effects of Postbiotic Mediators Derived from Lactobacillus rhamnosus GG and Lactobacillus reuteri on Streptococcus mutans. FBL. 2023;28(5):88. https://doi.org/10.31083/j.fbl2805088PMid:37258481 Chuah L-O, Foo HL, Loh TC, Mohammed Alitheen NB, Yeap SK, Abdul Mutalib NE, et al. Postbiotic metabolites produced by Lactobacillus plantarum strains exert selective cytotoxicity effects on cancer cells. BMC Complement Altern Med. 2019;19(1):114. https://doi.org/10.1186/s12906-019-2528-2PMid:31159791 PMCid:PMC6547513 Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. Methods. 2001;25(4):402-8. https://doi.org/10.1006/meth.2001.1262PMid:11846609 Aghebati-Maleki L, Hasannezhad P, Abbasi A, Khani N. Antibacterial, antiviral, antioxidant, and anticancer activities of postbiotics: a review of mechanisms and therapeutic perspectives. Biointerface Res Appl Chem. 2021;12:2629-45. https://doi.org/10.33263/BRIAC122.26292645 Hadad SE, Baik H, Alhebshi AM, Aburas M, Alrahimi J, Hassoubah S. Lactobacillus acidophilus' post biotic extracts combined with methotrexate regulated the levels of the apoptotic genes' expressions in the acute lymphoblastic leukemia cell line. Med Sci. 2022;26(122):1. https://doi.org/10.54905/disssi/v26i122/ms111e2020 Maftuni K, Zare P. Effects of Lactobacillus casei culture supernatant on differentiation of K562 cell line. Med Lab J. 2017;11(5):16-21. https://doi.org/10.29252/mlj.11.5.16 ZibasazTalebi A, Ahmadizadh C. The Study of Expression of Casp3/Bax Genes in HT29 Colon Cancer Cell Line with Lactobacillus rhamnosus Co-Culturing. J Ilam Univ Med Sci. 2020;28(4):25-35. https://doi.org/10.29252/sjimu.28.4.25 Hashemi-Khah MS, Arbab-Soleimani N, Forghanifard MM, Gholami O, Taheri S, Amoueian S. An In Vivo Study of Lactobacillus rhamnosus (PTCC 1637) as a New Therapeutic Candidate in Esophageal Cancer. Biomed Res Int. 2022;2022:7607470. https://doi.org/10.1155/2022/7607470PMid:35782061 PMCid:PMC9249511 Sadeghi-Aliabadi H, Mohammadi F, Fazeli H, Mirlohi M. Effects of Lactobacillus plantarum A7 with probiotic potential on colon cancer and normal cells proliferation in comparison with a commercial strain. Iran J Basic Med Sci. 2014;17(10):815-9. Zhong L, Li Y, Xiong L, Wang W, Wu M, Yuan T, et al. Small molecules in targeted cancer therapy: Advances, challenges, and future perspectives. Signal Transduct Target Ther. 2021;6(1):201. https://doi.org/10.1038/s41392-021-00572-wPMid:34054126 PMCid:PMC8165101 Afrin S, Giampieri F, Gasparrini M, Forbes-Hernández TY, Cianciosi D, Reboredo-Rodriguez P, et al. Dietary phytochemicals in colorectal cancer prevention and treatment: A focus on the molecular mechanisms involved. Biotechnol Adv. 2020;38:107322. https://doi.org/10.1016/j.biotechadv.2018.11.011PMid:30476540 Abbasi A, Rad AH, Maleki LA, Kafil HS, Baghbanzadeh A. Antigenotoxicity and Cytotoxic Potentials of Cell-Free Supernatants Derived from Saccharomyces cerevisiae var boulardii on HT-29 Human Colon Cancer Cell Lines. Probiotics Antimicrob Proteins. 2023:1-3. https://doi.org/10.1007/s12602-022-10039-1 Shyu PT, Oyong GG, Cabrera EC. Cytotoxicity of probiotics from Philippine commercial dairy products on cancer cells and the effect on expression of cfos and cjun early apoptotic-promoting genes and Interleukin-1 β and Tumor Necrosis Factor-α proinflammatory cytokine genes. Biomed Res Int. 2014;2014:491740. https://doi.org/10.1155/2014/491740PMid:25276792 PMCid:PMC4170743 Pfeffer CM, Singh AT. Apoptosis: a target for anticancer therapy. IJMS. 2018 Feb 2;19(2):448. https://doi.org/10.3390/ijms19020448PMid:29393886 PMCid:PMC5855670
