Isolated Lactobacillus fermentum Ab.RS۲۲ from traditional dairy products inhibits HeLa cervical cancer cell proliferation and modulates apoptosis by the PTEN-Akt pathway

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.RS۲۲ 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 ۰.۵, ۰.۷۵, ۱, ۱.۵, and ۲ ng/ml concentrations, and IC۵۰ values were detected by tetrazolium bromide. The L. fermentum Ab.RS۲۲-induced cell death by flow cytometry was confirmed through evaluation of the expression of caspase-۳, P۵۳, 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 ۲ ng/ml at ۲۴ hr (P<۰.۰۱); also, the IC۵۰ value was measured as ۱.۵ ng/ml. The findings of the flow cytometry assay showed that L. fermentum Ab.RS۲۲ in ۱.۵ ng/ml concentration at ۲۴ 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-۳, P۵۳, and PTEN genes was increased (P<۰.۰۱), and also expression of AKT gene (anti-apoptotic) was decreased (P<۰.۰۵). Conclusion: Our findings showed that L. fermentum Ab.RS۲۲ could dose-dependently inhibit the proliferation of the HeLa cells. Its apoptotic effect was confirmed via modulating PTEN/p۵۳/Akt gene expression and activation of the caspase-۳ mediated apoptosis pathway. Therefore, L. fermentum Ab.RS۲۲ can be considered a valuable anticancer candidate against cervical cancer progression in subsequent studies.

Keywords:

Apoptosis , Lactobacillus , Microbiology , Probiotics , PTEN protein , Tumor suppressor protein p۵۳