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

Objectives: 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.

Calcitriol modulates cholesteryl ester transfer protein (CETP) levels and lipid profile in hypercholesterolemic male rabbits: A pilot study.

Vitamin D3 efficacy against cardiovascular disease prevention has been reported in many experimental studies. We aimed to investigate the effect of the calcitriol or active form of Vitamin D3 (1, 25(OH) 2D3) on serum cholesteryl ester transfer protein (CETP) levels in a rabbit model of atherosclerosis. New Zealand white male rabbits were fed with 1% cholesterol diet and randomly assigned into two groups (n = 6). The case group was administrated with 50000 calcitriol (IU/kg/per wk) and the control group which administrated with calcitriol solvent (sesame oil) for 2 months. Then, after two months the lipid profile, CETP and 25OHD3 levels were measured. The serum concentration of CETP was increased after treatment with calcitriol in case group as compared to the control group (41.75 ± 3.19 vs. 34.5 ± 2.3, ng/ml, P < 0.05). We also observed higher levels of the 25OHD3 in the calcitriol group at the 1st month (16.3 ± 1.64 vs. 12.8 ± 1.33 ng/ml) and the 2nd month (19.5 ± 2.14 vs. 12.5 ± 1.25 ng/ml) as compared with the control group. the significant increase in the level of HDL-C was observed in the case group than the control group (P < 0.01). In addition, serum levels of LDL- Cholesterol (LDL-C), Triglyceride (TG) were reduced after assessment at 1st and 2nd month after administration of calcitriol. Our research indicated the significant anti-atherogenic effects of calcitriol in the rabbit model of atherosclerosis. However, increased in CETP levels by calcitriol may know as an additional way, which interfere with the anti-atherogenic effects of calcitriol.

Lactobacillus plantarum induces apoptosis in oral cancer KB cells through upregulation of PTEN and downregulation of MAPK signalling pathways.

Introduction: The oral tumor is the sixth most prevalent type of cancer worldwide and the second leading cause of cancer-related mortality. Although chemotherapy and immunotherapy are the main strategies for the treatment of oral cancer, an emergence of inevitable resistance to these treatment modalities is the major drawback that causes recurrence of the disease. Nowadays, probiotics have been suggested as adjunctive and complementary treatment modalities for improving the impacts of chemotherapy and immunotherapy agents. Probiotics, the friendly microflora in our bodies, contribute to the production of useful metabolites with positive effects on the immune system against various diseases such as cancer. Methods:Lactobacillus plantarum is one of the most important bacteria, which commensally live in the human oral system. In the current study, the impacts of L. plantarum on maintaining oral system health were investigated, and the molecular mechanisms of inhibition of oral cancer KB cells mediated by L. plantarum were evaluated using real-time polymerase chain reaction (PCR) and FACS flow cytometry analyses. Results: Our findings showed that L. plantarum is effective in the signal transduction of the oral cancer cells through upregulation and downregulation of PTEN and MAPK pathways, respectively. Conclusion: Based on the biological effects of oral candidate probiotics candidate bacterium L. plantarum on functional expression of PTEN and MAPK pathways, this microorganism seems to play a key role in controlling undesired cancer development in the oral system. Taken all, L. plantarum is proposed as a potential candidate for probiotics cancer therapy.

Enhancing antitumor activity of silver nanoparticles by modification with cell-penetrating peptides.

Recently, silver nanoparticles (AgNPs) have been used for cancer treatment. To achieve a successful anticancer activity, AgNP needs to be delivered sufficiently to the cells. Cell-penetrating peptides (CPPs) are small cationic peptides that have ability to transport various cargos across cell membranes. In this study, a strategy was developed for cancer treatment, where AgNP modified with CPPs displayed dramatically antitumor activity in MCF-7 cell lines. Peptides-modified AgNPs showed significant enhancement in killing tumor cells by increasing the uptake of AgNP into cell lines and could be a new class of nano-drug for cancer treatment.

Bovine lactoferrin ameliorates antioxidant esterase activity and 8-isoprostane levels in high-cholesterol-diet fed rats.

The main aim of the present study was to show the effect of bovineLactoferrin (bLF), an 80 kD iron-binding glycoprotein, its application on antioxidant esterase activities and 8-isoprostane changes in high-cholesterol-diet fed (HCD-Fed) rats. The 44 adult Sprague-Dawley male rats were randomly assigned into four experimental groups. They were randomly assigned into four equivalent groups (n = 11). The groups included the control group which was fed with normal diet, bLF group, the third group which were made hypercholesterolemia by being fed with high cholesterol diet, and the last group which consisted of hypercholesterolemia rats treated with bLF (HCD + bLF) for 4 weeks (200 mg.kg-1 per day wt. dissolved in 0.9% normal saline).After 4 weeks, the serum Paraoxonase1 (PON1), Arylesterase (ARE) activity and 8-isoprostane with lipid profile were measured. Upon treatment with the bLF, the decrease in LDL-Cholesterol (LDL-C), Glucoses, Triglyceride (TG) and Total-Cholesterol (TC) levels and an increase in HDL-Cholesterol (HDL-C) level were observed. The co-administration of bLf for 4 weeks had decreased the 8-isoprostane levels significantly (P < 0.001) (86.36 ± 7.1 vs 117.18 ± 8.62) when compared to hypercholesterolemia-induced rats. Also, the Atherogenic Index (AI) in HCD + bLF group showed a significant decrease as compared to the HCD group (P < 0.001) (0.37 ± 0.07 vs 0.57 ± 0.09). The results indicated that bLF was effective against oxidative stress by its ability to increase PON1 activity and reduce the lipid peroxidation in high-cholesterol-fed rats.