Characterization of the exopolysaccharides from Rhodotorula minuta IBRC-M 30135 and evaluation of their emulsifying, antioxidant and antiproliferative activities

Some microorganisms such as yeasts can produce high molecular weight and valuable polymers that known as exopolysaccharides (EPSs). Given the functional properties of yeast exopolysaccharides (EPSs) and a few numbers of studies in this field, the present study was aimed to characterize the EPSs from Rhodotorula minuta (IBRC-M 30135) and to evaluate their emulsifying, antioxidant and antiproliferative activities. R.minuta excreted 1.2 +/- 0.1 g of the EPSs per 1000 ml of fermentation medium. Glucose, mannose and rhamnose were found as main monosaccharides of the EPSs (49, 38 and 13 mol%, respectively) through gas chromatography-mass spectrometry (GC-MS) analysis. In addition, three EPS fractions were obtained with the molecular weights of 356, 500 and 220 kDa. The water retention capacity of the EPSs was 342 +/- 27%. The EPSs exhibited relatively good oil-emulsifying activity and the enhanced synergism between the R.minuta's EPSs and commercially used hydrocolloids (guar gum and sodium alginate) was observed. In vitro, antioxidant activity was investigated against DPPH, hydroxyl and superoxide free radicals. At a concentration of 10 mg/ml, the DPPH, hydroxyl and superoxide free radicals scavenging activities were 21.8 +/- 0.7%, 24.6 +/- 1.4% and 12.1 +/- 0.4%, respectively; and the scavenging activities against all were higher than hyaluronic acid. In addition, the treatment of human breast adenocarcinoma (MCF7) and Madin-Darby Canine Kidney (MDCK) cell lines with 20-1000 mu g/ml of the EPSs caused no significant differences in the cells proliferation (P>0.05). These results indicated the promising potential of the EPSs from R.minuta as non-toxic and biocompatible compounds for using in food, cosmetic and pharmaceutical fields

Anticancer Properties of Probiotic Saccharomyces boulardii Supernatant on Human Breast Cancer Cells

Saccharomyces boulardii, a variety of S. cerevisiae, is used as a probiotic yeast in food and drug industries. However, S. boulardii is an opportunistic pathogen, and the supernatant of this organism has recently been recommended for its healthpromoting benefts. Breast cancer is the most frequent cancer disease in women worldwide. The objective of this study was to investigate the efects of S. boulardii supernatant (SBS) on cell viability, inducing apoptosis and suppression of survivin gene expression in MCF-7 and MCF-7/MX as human non-drug-resistant and multidrug-resistant breast cancer cells respectively. The IC50 value of SBS against MCF-7 was calculated 1037, 542, and 543 µg/mL for 24, 48, and 72 h treatments, respectively. Also, this value against MCF-7/MX cells were measured 1242, 616, and 444 µg/mL after 24, 48, and 72 h respectively. We found that suppression of survivin gene expression should be one of the main molecular antitumor mechanisms which is contributed to apoptosis in breast cancer cells. However, anticancer activity of SBS was observed more efcient against MCF-7 than that against MCF-7/MX cells. SBS is suggested to be considered as one of the prospective anticancer drugs to treat human breast carcinoma. More investigations especially in vivo studies are strongly recommended to be implemented to characterize other antitumor mechanisms of SBS against breast carcinoma. Keywords Anticancer properties · Breast carcinoma · In vitro study · Probiotic Saccharomyces boulardii · Yeast supernatan

Enhancing the Therapeutic Efficacy of Daunorubicin and Mitoxantrone with Bavachinin, Candidone, and Tephrosin

The capability of flavonoids in sensitizing cancer cells was demonstrated in numerous works to chemotherapy and converse multidrug resistance by modulating efflux pumps and apoptosis mechanisms. Three flavonoids, namely, bavachinin, tephrosin, and candidone, have been recently introduced to cancer treatment research presenting various activities, such as antibacterial, immunomodulatory, cell death, and anticancer. Less information exists regarding the therapeutic significance of these flavonoids in cancer treatment, especially in overcoming multidrug resistance (MDR). Here, we tempted to investigate the potency of these agents in reversing MDR by analyzing their effects as chemosensitizers on cell cytotoxicity, P-gp and ABCG2 protein expression levels, and their function on two multidrug-resistant cell lines, P-gp-overexpressing human gastric adenocarcinoma cell line (EPG85.257RDB) and ABCG2-overexpressing human epithelial breast cancer cell line (MCF7/MX). The inhibitory concentration of 10% (IC10) of bavachinin, tephrosin, and candidone in EPG85.257RDB cells was 1588.7 ± 202.2, 264.8 ± 86.15, and 1338.6 ± 114.11 nM, respectively. Moreover, these values in MCF7/MX cell were 2406.4 ± 257.63, 38.8 ± 4.28, and 27.9 ± 5.59 nM, respectively. Expression levels of ABCG2 and P-gp were not significantly downregulated by these flavonoids. Maximum levels of daunorubicin and mitoxantrone accumulations and minimum rates of drug efflux in both cell lines were detected 48 hrs posttreatment with tephrosin and bavachinin, respectively. Chemosensitization to mitoxantrone and daunorubicin treatments was, respectively, achieved in MCF7/MX and EPG85.257RDB cells in response to IC10 of bavachinin and tephrosin, independently. These effects did not follow time-dependent manner, and each flavonoid had its cell-dependent patterns. Overall, bavachinin, tephrosin, and candidone showed potency to sensitize MDR cells to daunorubicin and mitoxantrone and could be considered as attractive MDR modulators for cancer treatment. However, their action was time and cell specific

Rapid Determination of Benzalkonium chloride in aqueous samples by FTIR spectroscopy in tandem with chemometrics

In this research, a powerful regression model coupled with FTIR spectroscopy (Mid, 800-1700 cm-1) has been proposed as an efficient method for precise determination of Benzalkonium chloride (BAK) in aqueous samples. For this purpose, both partial least squares regression (PLSR) and support vector regression (SVR) as methods of multivariate calibration were used for evaluation, and their results were compared. Accordingly, root mean square error of prediction, and leave-one-out cross-validation root mean square error, and correlation coefficients between the calculated ( R2 ) and the predicted ( ) values were used. In comparison to PLS

A novel insight into the cytotoxic effects of Tephrosin with calf thymus DNA: Experimental and in silico approaches

Tephrosin (TP) is a retinoid isoflavonoid that possesses various pharmacological and biological properties such as antitumor activity, anti-inflammatory, antimicrobial, anthelmintic, and anti-insect effects. In this work, the DNA binding characteristics of Tephrosin (TP) and its cytotoxic effect on cancer cell lines were investigated by the different techniques. The binding interaction between TP with calf thymus DNA (ctDNA) has been described using multispectroscopic methods and computational calculations. The results of UV�Visible absorption showed the occurrence of groove binding between TP and ctDNA, which was also supported by the results from a negligible change in CD signal and melting temperature (Tm), as well as the quenching effect of TP on DNA. Furthermore, various thermodynamic parameters revealed that the binding process was spontaneous and the main driving-forces were hydrophobic forces. Besides with this research, computational experiments showed that TP as a DNA binding agent, inserted into the minor groove of B-DNA fragment with a C-G rich region, and forming a stable complex. MTT analysis of TP against MCF-7 cell lines represented a high cytotoxic effect

Resistance of human primary mesenchymal stem cells to cytotoxic effects of nutlin‐3 in vitro

Background The small-molecule nutlin-3 was found to be an effective therapeutic compound and p53 activator, and acts as a murine double minute 2 antagonist, although these findings need to be clinically confirmed. The essential components of the bone marrow include mesenchymal stem cells (MSCs), which play a key role in protecting, regenerating, and proliferating hematopoietic stem cells (HSCs). This feature is vital for HSC after exposure to myelotoxic anticancer agents; nevertheless, the effects of nutlin-3 on MSCs remain to be disclosed. The present research study was conducted to examine the antiproliferative and proapoptotic effectiveness of nutlin-3 in bone marrow MSCs (BMSCs). Materials and Methods Human-derived BMSCs were cultured for different durations, that is, 24, 48, and 72 hours, and treated using various concentrations of nutlin-3, including 5, 10, 25, 50, and 100 mu M. To investigate the effect of nutlin-3 on the apoptosis, cell vitality and proliferation in BMSCs, the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), thiazolyl blue tetrazolium bromide, propidium iodide (PI) and annexin V assay, as well as real-time polymerase chain reaction, were used. Results BMSCs viability significantly decreased (P < .05) in the cells treated at concentrations of 50 and 100 mu M for 24 hours and concentrations of 25, 50, and 100 mu M for 48 hours and at all concentrations for 72 hours. The apoptosis of BMSCs (TUNEL positive) was significantly more visible at concentrations of 25 and 50 mu M compared with that in the controls (P < .05), while this increased through dose-dependent processes. Annexin V/PI staining revealed negligible dose-dependent increases in all the apoptotic cells after 72 hours of incubation, and this apoptosis elevation was significant at 25 and 50 mu M (P < .05). Conclusion Resistance to nutlin-3 was observed in human bone marrow-derived MSCs; nevertheless, further clinical data are required to be obtained with long-duration exposure to confirm the present findings

Probiotic Saccharomyces cerevisiae var. boulardii supernatant inhibits survivin gene expression and induces apoptosis in human gastric cancer cells

Natural anticancer drug and compounds with other great benefits are of interest recently due to lower side effects than chemotherapy for cancer treatment and prevention. Different natural and synthetic drugs have been suggested to be used for treatment of gastric cancers, the second deadly cancer worldwide. The aim of this study was to investigate anticancer activity of SBS including inducing apoptosis and inhibition of survivin gene expression in gastric cancer cells. We evaluated cell viability, inducing apoptosis and change in survivin gene expression of EPG85-257P (EPG) and EPG85-257RDB (resistant to Daunorubicin, RDB) cell lines under exposure of SBS after 24, 48, and 72 hr. We found that SBS decreased cell viability, induced apoptosis, and reduced survivin gene expression in treated EPG and RDB cells (with the significant IC50 values of 387 and 575 μg/ml after 72 and 48 hr for EPG and RDB cells respectively). However, we observed SBS was more efficient to induce apoptosis in EPG than RDB cells. We strongly suggest SBS be considered as a prospective anticancer agent or in formulation of complementary medication to treat and prevent gastric cancers

Deciphering the DNA-binding affinity, cytotoxicity and apoptosis induce as the anticancer mechanism of Bavachinin: An experimental and computational investigation

One of the most important mechanism by which bioflavonoids can exert their effects in cancer treatment, is through their interaction with bio-macromolecules such as DNA. Recent literature emphasizes the role of Bavachinin (BVC) as an emerging anticancer agent. However, there are no reports on its ability to interact with DNA. The present study investigated the DNA binding properties of BVC by many spectroscopic and computational approaches. The evidences are provided from UV–visible and CD spectral analyses illustrated that BVC interacted with ctDNA through minor groove binding mode. Based on the thermodynamic analyses, it can be inferred that the binding process was spontaneous, and the hydrophobic interaction played a major role in BVC-ctDNA binding. In silico molecular docking and dynamic simulation finally strengthened our experimental results that BVC was located in the minor groove (AT- rich) region of B-DNA structure and resulted in the slight alteration in the secondary structure of DNA during the interaction process. Additionally, BVC indicated significant cytotoxicity against MCF-7 breast cancer cells. Furthermore, quantitative analyses demonstrate that BVC treatment significantly increased the expression of pro-apoptotic genes; p53, caspase-3, -8, and -9 in MCF-7 cells. In order to further investigate the molecular targets of BVC, molecular docking studies indicated a relatively good binding affinity of BVC with pro-apoptotic proteins. In effect, BVC can be considered as a small organic compound with DNA binding property, appropriate cytotoxic activity, and potential of apoptotic inducing that can be adopted for medical science and pharmacy

Biosynthesis of exopolysaccharide from waste molasses using <i>Pantoea </i>sp. BCCS 001 GH:a kinetic and optimization study

The bacterium Pantoea sp. BCCS 001 GH produces an exopolysaccharide (EPS) named Pantoan through using sugar beet molasses (SBM) as an inexpensive and widely available carbon source. This study aims to investigate the kinetics and optimization of the Pantoan biosynthesis using Pantoea sp. BCCS 001 GH in submerged culture. During kinetics studies, the logistic model and Luedeking–Piret equation are precisely fit with the obtained experimental data. The response surface methodology (RSM)-central composite design (CCD) method is applied to evaluate the effects of four factors (SBM, peptone, Na2HPO4, and Triton X-100) on the concentration of Pantoan in batch culture of Pantoea sp. BCCS 001 GH. The experimental and predicted maximum Pantoan production yields are found 9.9 ± 0.5 and 10.30 g/L, respectively, and the best prediction factor concentrations are achieved at 31.5 g/L SBM, 2.73 g/L peptone, 3 g/L Na2HPO4, and 0.32 g/L Triton X-100 after 48 h of submerged culture fermentation, at 30 °C. The functional groups and major monosaccharides (glucose and galactose) of a purified Pantoan are described and confirmed by 1HNMR and FTIR. The produced Pantoan is also characterized by thermogravimetric analysis and the rheological properties of the biopolymer are investigated. The present work guides the design and optimization of the Pantoea sp. BCCS 001 GH culture media, to be fine-tuned and applied to invaluable EPS, which can be applicable in food and biotechnology applications.SCOPUS: ar.jinfo:eu-repo/semantics/publishe