Volume 27, Issue 2 (July 2023)                   Physiol Pharmacol 2023, 27(2): 202-210 | Back to browse issues page

XML Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Mousavi Esfahani S M, Rashidi N, Abkhiz S, Akbari N, tarighi P. Local probiotic Lactobacillus brevis downregulates LPAR1 and LPAR2 gene expression and reduces invasion of MDA-MB-231 and MCF-7 breast cancer cell lines. Physiol Pharmacol 2023; 27 (2) :202-210
URL: http://ppj.phypha.ir/article-1-1936-en.html
Abstract:   (710 Views)

Introduction: Breast cancer (BC) is the second leading cause of cancer deaths in the world. Studies suggest that the lysophosphatidic acid (LPA) gene is the cause of invasion and metastasis in malignant cancers, including BC. In addition, the PI3K/ PAK1/ ERK cascade in cancer cells helps metastatic BC. It has been observed that LPA can stimulate reactive oxygen species production, which is an important mediator of LPA to stimulate the migration of BC cells and activate the PI3K/ PAK1/ ERK signaling pathway.
Methods: This study aimed to evaluate the Lactobacillus brevis probiotic supernatant’s effectiveness in reducing LPA expression in BC cell lines. MCF-7 and MDA-MB-231 cell lines were treated with supernatant of local Lactobacillus brevis for 24 and 48h. mRNA expression levels of LPAR1 and LPAR2 genes were evaluated by qRT-PCR. Furthermore, an invasion assay was performed to assess these cell lines’ invasion rate following treatment.
Results: The results indicated a remarkable decline in the survival rate of treated cells. LPAR1 and LPAR2 gene expression declined in MDA-MB-231 and MCF-7 cells. Moreover, the invasion rate of these cells was reduced following treatment.
Conclusion: Considering Lactobacillus brevis supernatant’s cytotoxic effects on cancerous cells, this bacteria could be thought of as a promising application for a possible treatment approach with fewer adverse reactions. However, more research is obviously needed. In the future, probiotics could be used in conjunction with currently available therapies.

Full-Text [PDF 1090 kb]   (215 Downloads)    

1. Abedin-Do A, Taherian-Esfahani Z, Ghafouri-Fard S, Ghafouri-Fard S, Motevaseli E. Immunomodulatory effects of Lactobacillus strains: emphasis on their effects on cancer cells. Immunotherapy 2015; 7: 1307-29. [DOI:10.2217/imt.15.92]
2. Al-Oqail MM, Al-Sheddi ES, Farshori NN, Al-Massarani SM, Al-Turki EA, Ahmad J, et al. Corn silk (Zea mays L.) induced apoptosis in human breast cancer (MCF-7) cells via the ROS-mediated mitochondrial pathway. Oxid Med Cell Longev 2019; 2019. [DOI:10.1155/2019/9789241]
3. 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: 185-96. [DOI:10.1097/CJI.0000000000000079]
4. Boucharaba A, Serre CM, Guglielmi J, Bordet JC, Clézardin P, Peyruchaud O. The type 1 lysophosphatidic acid receptor is a target for therapy in bone metastases. Proc Natl Acad Sci U S A 2006;103: 9643-8. [DOI:10.1073/pnas.0600979103]
5. Chen GY, Cleary JM, Asenjo AB, Chen Y, Mascaro JA, Arginteanu DF, et al. Kinesin-5 promotes microtubule nucleation and assembly by stabilizing a lattice-competent conformation of tubulin. Curr Biol 2019; 29: 2259-69. [DOI:10.1016/j.cub.2019.05.075]
6. Chen M, Towers LN, O’Connor KL. LPA2 (EDG4) mediates Rho-dependent chemotaxis with lower efficacy than LPA1 (EDG2) in breast carcinoma cells. Am J Physiol Cell Physiol 2007; 292: C1927-33. [DOI:10.1152/ajpcell.00400.2006]
7. Choi JW, Herr DR, Noguchi K, Yung YC, Lee CW, Mutoh T, et al. LPA receptors: subtypes and biological actions. Annu Rev Pharmacol Toxicol 2010; 50: 157-86. [DOI:10.1146/annurev.pharmtox.010909.105753]
8. Coulup SK, Georg GI. Revisiting microtubule targeting agents: α-Tubulin and the pironetin binding site as unexplored targets for cancer therapeutics. Bioorg Med Chem Lett 2019; 29: 1865-73. [DOI:10.1016/j.bmcl.2019.05.042]
9. Daniluk U. Probiotics, the new approach for cancer prevention and/or potentialization of anti-cancer treatment. J Clin Exp Oncol 2012; 1:2. [DOI:10.4172/2324-9110.1000e105]
10. Dimitrovski D, Cencič A, Winkelhausen E, Langerholc T. Lactobacillus plantarum extracellular metabolites: in vitro assessment of probiotic effects on normal and cancerogenic human cells. Int Dairy J 2014; 39: 293-300. [DOI:10.1016/j.idairyj.2014.07.009]
11. Dong C, Beltcheva M, Gontarz P, Zhang B, Popli P, Fischer LA, et al. Derivation of trophoblast stem cells from naïve human pluripotent stem cells. Elife 2020; 9: e52504. [DOI:10.7554/eLife.52504]
12. Du J, Sun C, Hu Z, Yang Y, Zhu Y, Zheng D, et al. Lysophosphatidic acid induces MDA-MB-231 breast cancer cells migration through activation of PI3K/PAK1/ERK signaling. PloS one 2010; 5: e15940. [DOI:10.1371/journal.pone.0015940]
13. Escamilla J, Lane MA, Maitin V. Cell-free supernatants from probiotic Lactobacillus casei and Lactobacillus rhamnosus GG decrease colon cancer cell invasion in vitro. Nutr Cancer 2012; 64: 871-8. [DOI:10.1080/01635581.2012.700758]
14. Feyereisen M, Mahony J, Kelleher P, Roberts RJ, O’Sullivan T, Geertman JM, et al. Comparative genome analysis of the Lactobacillus brevis species. BMC genomics 2019; 20: 416. [DOI:10.1186/s12864-019-5783-1]
15. Geraldo LH, Spohr TC, Amaral RF, Fonseca AC, Garcia C, Mendes FD, et al. Role of lysophosphatidic acid and its receptors in health and disease: novel therapeutic strategies. Signal Transduct Target Ther 2021; 6: 45. [DOI:10.1038/s41392-020-00367-5]
16. Górska A, Przystupski D, Niemczura MJ, Kulbacka J. Probiotic bacteria: a promising tool in cancer prevention and therapy. Curr Microbiol 2019; 76: 939-49. [DOI:10.1007/s00284-019-01679-8]
17. Jafari-Nasab T, Khaleghi M, Farsinejad A, Khorrami S. Probiotic potential and anticancer properties of Pediococcus sp. isolated from traditional dairy products. Biotechnol Rep (Amst) 2021; 29: e00593. [DOI:10.1016/j.btre.2021.e00593]
18. Kamkar F, Haghighat S, Mahdavi M. Secreted chemicals from probiotic bacteria potentiate Th1 pattern of immune cells and apoptosis induction in breast cancer and gastric adenocarcinoma cell lines. Immunoregulation 2020; 3: 15-28. [DOI:10.32598/IMMUNOREGULATION.3.1.2]
19. Kang HJ, Im SH. Probiotics as an immune modulator. J Nutr Sci Vitaminol (Tokyo) 2015; 61: S103-5. [DOI:10.3177/jnsv.61.S103]
20. Karimi-Maleh H, Karimi F, Malekmohammadi S, Zakariae N, Esmaeili R, Rostamnia S, et al. An amplified voltammetric sensor based on platinum nanoparticle/polyoxometalate/two-dimensional hexagonal boron nitride nanosheets composite and ionic liquid for determination of N-hydroxysuccinimide in water samples. J Mol Liq 2020; 310: 113185. [DOI:10.1016/j.molliq.2020.113185]
21. Marinelli L, Tenore GC, Novellino E. Probiotic species in the modulation of the anticancer immune response. I Semin Cancer Biol 2017; 46: 182-90. [DOI:10.1016/j.semcancer.2017.08.007]
22. Markowiak P, Śliżewska K. Effects of probiotics, prebiotics, and synbiotics on human health. Nutrients 2017; 9: 1021. [DOI:10.3390/nu9091021]
23. Mills GB, Moolenaar WH. The emerging role of lysophosphatidic acid in cancer. Nat Rev Cancer 2003; 3: 582-91. [DOI:10.1038/nrc1143]
24. Mogna L, Mogna G. Innovative probiotics and systemic bioactive metabolites. Anti-ageing potential. Nutrafoods 2012; 11: 151-64. [DOI:10.1007/s13749-012-0057-4]
25. 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: 66-76.
26. Nasiri Z, Montazeri H, Akbari N, Mirfazli SS, Tarighi P. Synergistic cytotoxic and apoptotic effects of local probiotic Lactobacillus brevis isolated from regional dairy products in combination with tamoxifen. Nutr Cancer 2021; 73: 290-9. [DOI:10.1080/01635581.2020.1743871]
27. Pan X, Chen F, Wu T, Tang H, Zhao Z. The acid, bile tolerance and antimicrobial property of Lactobacillus acidophilus NIT. Food Control 2009; 20: 598-602. [DOI:10.1016/j.foodcont.2008.08.019]
28. Pandey KR, Naik SR, Vakil BV. Probiotics, prebiotics and synbiotics-a review. J Food Sci Technol 2015; 52: 7577-87.
29. Plastira I, Bernhart E, Joshi L, Koyani CN, Strohmaier H, Reicher H, et al. MAPK signaling determines lysophosphatidic acid (LPA)-induced inflammation in microglia. J Neuroinflammation 2020; 17: 127. [DOI:10.1186/s12974-020-01809-1]
30. Ramakrishna BS. Probiotic-induced changes in the intestinal epithelium: implications in gastrointestinal disease. Trop Gastroenterol 2009; 30: 76-85.
31. Shamsadin-Azad Z, Taher MA, Cheraghi S, Karimi-Maleh H. A nanostructure voltammetric platform amplified with ionic liquid for determination of tert-butylhydroxyanisole in the presence kojic acid. J Food Me:as char:act 2019; 13: 1781-7. [DOI:10.1007/s11694-019-00096-6]
32. Song S, Oh S, Lim KT. The proteins (12 and 15 kDa) isolated from heat-killed Lactobacillus plantarum L67 induces apoptosis in HT-29 cells. Cell Biochem Funct 2015; 33: 89-96. [DOI:10.1002/cbf.3094]
33. Thiagarajan PS, Sinyuk M, Turaga SM, Mulkearns-Hubert EE, Hale JS, Rao V,et al. Cx26 drives self-renewal in triple-negative breast cancer via interaction with NANOG and focal adhesion kinase. Nat. Commun 2018; 9:1-14. [DOI:10.1038/s41467-018-02938-1]
34. Toyomane K, Yokota R, Watanabe K, Akutsu T, Asahi A, Kubota S. Optimization of microbial DNA extraction from human skin samples for CRISPR typing. Forensic Sci Int Rep 2022; 5: 100259. [DOI:10.1016/j.fsir.2022.100259]
35. Yang X, Da M, Zhang W, Qi Q, Zhang C, Han S. Role of Lactobacillus in cervical cancer. Cancer Manag Res 2018; 10: 1219-29. [DOI:10.2147/CMAR.S165228]
36. Yu AQ, Li L. The potential role of probiotics in cancer prevention and treatment. Nutr Cancer 2016; 68: 535-44. [DOI:10.1080/01635581.2016.1158300]
37. Zandi M, Ebrahimifard M. Evaluation of miR-101 Level in patients with chronic hepatitis B virus infection and liver cirrhosis. Med Lab J 2017; 11: 10-4.
38. Zhang Z, Lv J, Pan L, Zhang Y. Roles and applications of probiotic Lactobacillus strains. Appl Microbiol Biotechnol 2018; 102: 8135-43. [DOI:10.1007/s00253-018-9217-9]
39. Zhuang J, Nie G, Yang F, Dai X, Cao H, Xing C, et al. Cadmium induces cytotoxicity through oxidative stress-mediated apoptosis pathway in duck renal tubular epithelial cells. Toxicol In Vitro 2019; 61:104625. [DOI:10.1016/j.tiv.2019.104625]

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.