Volume 27, Issue 4 (December 2023)                   Physiol Pharmacol 2023, 27(4): 426-434 | Back to browse issues page


XML Print


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

Samiei Mosleh I, Karami F, Salahshourifar I, Tajabadi Ebrahimi M, Marvibaigi M. Investigating the effects of Lactobacillus acidophilus and Lactobacillus paracasei supernatant on cervical cancer cells. Physiol Pharmacol 2023; 27 (4) : 8
URL: http://ppj.phypha.ir/article-1-1900-en.html
Abstract:   (1555 Views)

Introduction: Lactic acid bacteria, recognized as probiotics, have garnered significant attention as potential adjuvants in chemotherapy for various cancer types, including cervical cancer. In this study, we investigated the anti-cancer properties of two indigenous Iranian strains, Lactobacillus acidophilus and Lactobacillus paracasei, individually and in combination, targeting human cervical cancer cell lines compared to normal control cells.
Methods: The cytotoxic effect of Lactobacillus acidophilus and Lactobacillus paracasei supernatants, as well as their 1:1 mixture, on CaSki and HNCF PI 52 cell lines, was evaluated using the MTT assay. The apoptotic and anti-metastatic effects of these supernatants were assessed by analyzing the gene expression of BAX/BCL2 ratio, Caspase-3, and MMP2/ MMP9 using Real-Time Reverse Transcriptase Polymerase Chain Reaction (RT-PCR).
Results: Significant cytotoxicity was observed in Ca Ski cells attributed to the low pH of the supernatants. The increase in the BAX/BCL2 ratio, leading to an up-regulation of Caspase-3, indicated the induction of apoptosis (P<0.001). In addition, the expression of MMP9 significantly deceased in Ca Ski cells treated with Lactobacillus acidophilus (P<0.001) and Lactobacillus paracasei (P<0.05), while no significant difference in MMP2 expression was observed in all samples compared to the control groups.
Conclusion: while further validation is needed, the heightened expression of apoptotic genes suggests a potential induction of apoptosis in cancer cells in response to Lactobacillus toxicity. The significant down-regulation of the MMP9 gene emphasizes the need for comparative analyses across different cervical cancer cell lines to establish the anti-metastatic potential of these local probiotic supernatants.

Article number: 8
Full-Text [PDF 1052 kb]   (531 Downloads)    

References
1. Aminaei M, Karami F, Marvibaigi M, Sotoodehnejadnematalahi F, Tajabadi Ebrahimi M. Primary evidence on the potential of Lactobacillus paracasei in treatment of hepatocellular carcinoma. Food and Health 2018; 3: 27-9.
2. Badgeley A, Anwar H, Modi K, Murphy P, Lakshmikuttyamma A. Effect of probiotics and gut microbiota on anti-cancer drugs: Mechanistic perspectives. Biochim Biophys Acta Rev Cancer 2021; 1875: 188494. [DOI:10.1016/j.bbcan.2020.188494]
3. Chao X, Song X, Wu H, You Y, Wu M, Li L. Selection of treatment regimens for recurrent cervical cancer. Front Oncol 2021; 11: 618485. [DOI:10.3389/fonc.2021.618485]
4. Chee WJY, Chew SY, Than LTL. Vaginal microbiota and the potential of Lactobacillus derivatives in maintaining vaginal health. Microb Cell Fact 2020; 19: 203. [DOI:10.1186/s12934-020-01464-4]
5. Gerl R, Vaux DL. Apoptosis in the development and treatment of cancer. Carcinogenesis 2005; 26: 263-70. [DOI:10.1093/carcin/bgh283]
6. Górska A, Przystupski D, Niemczura M J, Kulbacka J. Probiotic bacteria: A promising tool in cancer prevention and therapy. Curr Microbiol 2019; 76: 939-949. [DOI:10.1007/s00284-019-01679-8]
7. Huang Q, Li F, Liu X, Li W, Shi W, Liu FF, et al. Caspase 3-mediated stimulation of tumor cell repopulation during cancer radiotherapy. Nat Med 2011; 17: 860-6. [DOI:10.1038/nm.2385]
8. Isazadeh A, Hajazimian S, Shadman B, Safaei S, Babazadeh Bedoustani A, Chavoshi R, et al. Anti-cancer effects of probiotic lactobacillus acidophilus for colorectal cancer cell line Caco-2 through apoptosis induction. Pharm Sci 2021; 27: 262-7. [DOI:10.34172/PS.2020.52]
9. Kim SN, Lee WM, Park KS, Kim JB, Han DJ, Bae J. The effect of Lactobacillus casei extract on cervical cancer cell lines. Contemp Oncol (Pozn) 2015; 19: 306-12. [DOI:10.5114/wo.2014.45292]
10. Li X, Wang H, Du X, Yu W, Jiang J, Geng Y, et al. Lactobacilli inhibit cervical cancer cell migration in vitro and reduce tumor burden in vivo through upregulation of E-cadherin. Oncol Rep 2017; 38: 1561-8. [DOI:10.3892/or.2017.5791]
11. Markowiak P, Śliżewska K. Effects of probiotics, prebiotics, and synbiotics on human health. Nutrients 2017; 9. [DOI:10.3390/nu9091021]
12. Mirzayi C, Renson A, Zohra F, Elsafoury S, Geistlinger L, Kasselman LJ, et al. Reporting guidelines for human microbiome research: the STORMS checklist. Nat Med 2021; 27: 1885-92. [DOI:10.1038/s41591-021-01552-x]
13. Motevaseli E, Azam R, Akrami SM, Mazlomy M, Saffari M, Modarressi M H, et al. The effect of lactobacillus crispatus and lactobacillus rhamnosus culture supernatants on expression of autophagy genes and HPV E6 and E7 oncogenes in the HeLa cell line. Cell J 2016; 17: 601-7.
14. Motevaseli E, Shirzad M, Akrami SM, Mousavi AS, Mirsalehian A, Modarressi M H. Normal and tumour cervical cells respond differently to vaginal lactobacilli, independent of pH and lactate. J Med Microbiol 2013; 62: 1065-72. [DOI:10.1099/jmm.0.057521-0]
15. Nouri Z, Karami F, Neyazi N, Modarressi MH, Karimi R, Khorramizadeh MR, et al. Dual anti-metastatic and anti-proliferative activity assessment of two probiotics on HeLa and HT-29 cell lines. Cell J 2016; 18: 127-34.
16. Riaz Rajoka MS, Zhao H, Lu Y, Lian Z, Li N, Hussain N, et al. Anticancer potential against cervix cancer (HeLa) cell line of probiotic Lactobacillus casei and Lactobacillus paracasei strains isolated from human breast milk. Food Funct 2018; 9: 2705-15. [DOI:10.1039/C8FO00547H]
17. Ryoo HD, Bergmann A. The role of apoptosis-induced proliferation for regeneration and cancer. Cold Spring Harb Perspect Biol 2012; 4: a008797. [DOI:10.1101/cshperspect.a008797]
18. 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: 815-9.
19. Schröpfer A, Kammerer U, Kapp M, Dietl J, Feix S, Anacker J. Expression pattern of matrix metalloproteinases in human gynecological cancer cell lines. BMC Cancer 2010; 10: 553. [DOI:10.1186/1471-2407-10-553]
20. Sharma V, Kaur R, Bhatnagar A, Kaur J. Low-pH-induced apoptosis: role of endoplasmic reticulum stress-induced calcium permeability and mitochondria-dependent signaling. Cell Stress Chaperones 2015; 20: 431-40. [DOI:10.1007/s12192-014-0568-6]
21. Sung H, Ferlay J, Siegel R L, 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. [DOI:10.3322/caac.21660]
22. Tsakmaklis A, Vehreschild M, Farowski F, Trommer M, Kohler C, Herter J, et al. Changes in the cervical microbiota of cervical cancer patients after primary radio-chemotherapy. Int J Gynecol Cancer 2020; 30: 1326-30. [DOI:10.1136/ijgc-2019-000801]
23. Wang KD, Xu DJ, Wang BY, Yan DH, Lv Z, Su JR. Inhibitory effect of vaginal lactobacillus supernatants on cervical cancer cells. Probiotics Antimicrob Proteins 2018; 10: 236-42. [DOI:10.1007/s12602-017-9339-x]
24. Wen H, Guo Q-H, Zhou X-L, Wu X-H, Li J. Genomic profiling of chinese cervical cancer patients reveals prevalence of DNA damage repair gene alterations and related hypoxia feature. Front Oncol 2022; 11: 792003. [DOI:10.3389/fonc.2021.792003]

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