Isolated Lactobacillus fermentum Ab.RS22 from traditional dairy products inhibits HeLa cervical cancer cell proliferation and modulates apoptosis by the PTEN-Akt pathway

Document Type : Original Article


1 INSERM U1148, Laboratory for Vascular Translation Science (LVTS), Cardiovascular Bioengineering, University Sorbonne Paris North, Paris, France

2 Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran

3 Clinical Research Development Unit, Booalisina Hospital, Qazvin University of Medical Sciences, Qazvin, Iran

4 Student Research Committee, Qazvin University of Medical Sciences, Qazvin, Iran

5 Clinical Pharmacist, Baylor Scott & White Medical Center – Lakeway 100 Medical Pkwy, Lakeway, TX 78738

6 Rayan Novin Pajoohan Pras, Biotechnology Company, Biotechnology Incubator, Shiraz University of Medical Sciences, Shiraz, Iran

7 Medical Microbiology Research Center, Qazvin University of Medical Sciences, Qazvin, Iran

8 Department of Medical Parasitology and Mycology, School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran

9 Department of Biochemistry and Genetics, School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran


Objective(s): It is worthwhile to note that, some probiotics such as Lactobacilli and Bifidobacteria isolated from dairy products have significant therapeutic effects against cancer cells. Here, we evaluated anti-proliferation and the apoptotic effects of isolated Lactobacillus fermentum Ab.RS22 from traditional dairy products on the HeLa cervical cancer cells in vitro.
Materials and Methods: The viability of treated HeLa cells with supernatant of Lactobacillus in 0.5, 0.75, 1, 1.5, and 2 ng/ml concentrations, and IC50 values were detected by tetrazolium bromide. The L. fermentum Ab.RS22-induced cell death by flow cytometry was confirmed through evaluation of the expression of caspase-3, P53, PTEN, and AKT genes by quantitative reverse transcription-polymerase chain reactions (qRT-PCR).
Results: Most cytotoxicity effects of Lactobacillus on HeLa cells were detected in 2 ng/ml at 24 hr (P<0.01); also, the IC50 value was measured as 1.5 ng/ml. The findings of the flow cytometry assay showed that L. fermentum Ab.RS22 in 1.5 ng/ml concentration at 24 hr increased the percentage of both apoptosis and necrosis cells. Lactobacillus-induced cell death was verified through results of Real-time PCR; where expression of caspase-3, P53, and PTEN genes was increased (P<0.01), and also expression of AKT gene (anti-apoptotic) was decreased (P<0.05). 
Conclusion: Our findings showed that L. fermentum Ab.RS22 could dose-dependently inhibit the proliferation of the HeLa cells. Its apoptotic effect was confirmed via modulating PTEN/p53/Akt gene expression and activation of the caspase-3 mediated apoptosis pathway. Therefore, L. fermentum Ab.RS22 can be considered a valuable anticancer candidate against cervical cancer progression in subsequent studies. 


Main Subjects

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