Anticancer activity of lactoferrin-coated biosynthesized selenium nanoparticles for combating different human cancer cells via mediating apoptotic effects.

The present study aims to develop a novel nanocombination with high selectivity against several invasive cancer cells, sparing normal cells and tissues. Bovine lactoferrin (bLF) has recently captured the interest of numerous medical fields owing to its biological activities and well-known immunomodulatory effects. BLF is an ideal protein to be encapsulated or adsorbed into selenium nanocomposites (Se NPs) in order to produce stable nanocombinations with potent anticancer effects and improved immunological functions. The biosynthesis of the functionalized Se NPs was achieved using Rhodotorula sp. strain MZ312359 via a simultaneous bio-reduction approach to selenium sodium salts. The physicochemical properties of Se NPs using SEM, TEM, FTIR, UV Vis, XRD, and EDX confirmed the formation of uniform agglomerated spheres with a size of 18-40 nm. Se NPs were successfully embedded in apo-LF (ALF), forming a novel nanocombination of ALF-Se NPs with a spherical shape and an average nanosize of less than 200 nm. The developed ALF-Se NPs significantly displayed an effective anti-proliferation efficiency against many cancer cells, including MCF-7, HepG-2, and Caco-2 cell lines, as compared to Se NPs and ALF in free forms. ALF-Se NPs showed a significant selectivity impact (> 64) against all treated cancer cells at IC50 63.10 ≤ µg/mL, as well as the strongest upregulation of p53 and suppression of Bcl-2, MMP-9, and VEGF genes. Besides, ALF-Se NPs were able to show the maximum activation of transcrition of key redox mediator (Nrf2) with suppression in reactive oxygen species (ROS) levels inside all treated cancer cells. This study demonstrates that this novel nanocombination of ALF-Se NPs has superior selectivity and apoptosis-mediating anticancer activity over free ALF or individual form of Se NPs.

Antioxidant, Anti-Inflammatory, Antimicrobial, and Anticancer Activities of Pomegranate Juice Concentrate.

Pomegranate juice concentrate (PJC) is a rich source of polyphenols, which exhibit significant antioxidant activity and potential health benefits for disease prevention and therapy. In this study, the polyphenolic profile of PJC was investigated for the first time, and it was found that PJC can inhibit oxidative damage to bovine serum albumin (BSA) and deoxyribonucleic acid (DNA), as well as acetylcholinesterase, α-amylase, and tyrosinase activities. The primary polyphenols identified in PJC were 4-Hydroxy-3-Methoxybenzoate, epicatechin, catechin, rutin, ferulic acid, P-coumaric acid, and cinnamic acid. Additionally, PJC demonstrated potent antibacterial effects against human pathogens such as Streptococcus mutans and Aeromonas hydrophila and dose-dependently reduced the proliferation of colorectal, breast, and hepatic cancer cells via apoptosis. Furthermore, PJC blocked B-cell lymphoma 2 (BCl-2) and the expression of a potent cyclin-dependent kinase inhibitor (P21) and enhanced tumor protein (P53) expression, compared to both untreated cells and cells treated with fluoropyrimidine 5-fluorouracil (5-FU). As a result, PJC may be a beneficial ingredient in the formulation of emerging natural-compound-based chemotherapy and functional foods and could be utilized by the food, nutraceutical, and pharmaceutical industries.

Palm Fruit (Phoenix dactylifera L.) Pollen Extract Inhibits Cancer Cell and Enzyme Activities and DNA and Protein Damage.

Palm fruit pollen extract (PFPE) is a natural source of bioactive polyphenols. The primary aim of the study was to determine the antioxidant, antimicrobial, anticancer, enzyme inhibition, bovine serum albumin (BSA), and DNA-protective properties of PFPE and identify and quantify the phenolic compounds present in PFPE. The results demonstrated that PFPE exhibited potent antioxidant activity in various radical-scavenging assays, including (2,2-diphenyl-1-picrylhydrazyl) (DPPH•), 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS•), nitric oxide (NO), ferric-reducing/antioxidant power (FRAP), and total antioxidant capacity (TAC). PFPE also displayed antimicrobial activity against several pathogenic bacteria. Similarly, PFPE reduced acetylcholinesterase, tyrosinase, and α-amylase activities. PFPE has been proven to have an anticancer effect against colon carcinoma (Caco-2), hepatoma (HepG-2), and breast carcinoma (MDA) cancer cells. Apoptosis occurred in PFPE-treated cells in a dose-dependent manner, and cell cycle arrest was observed. Furthermore, in breast cancer cells, PFPE down-regulated Bcl-2 and p21 and up-regulated p53 and Caspase-9. These results show that PFPE constitutes a potential source of polyphenols for pharmaceutical, nutraceutical, and functional food applications.

Scaling-up strategies for controllable biosynthetic ZnO NPs using cell free-extract of endophytic Streptomyces albus: characterization, statistical optimization, and biomedical activities evaluation.

In this study, we identified a suitable precursor and good cellular compartmentalization for enhancing bioactive metabolites to produce biosynthetic zinc oxide nanoparticles (ZnO NPs). An effective medium for cultivating endophytic Streptomyces albus strain E56 was selected using several optimized approaches in order to maximize the yield of biosynthetic ZnO NPs. The highest biosynthetic ZnO NPs yield (4.63 g/L) was obtained when pipetting the mixed cell-free fractions with 100 mM of zinc sulfate as a precursor. The generation of biosynthetic ZnO NPs was quickly verified using a colored solution (white color) and UV-Visible spectroscopy (maximum peak, at 320 nm). On a small scale, the Taguchi method was applied to improve the culture medium for culturing the strain E56. As a result, its cell-dry weight was 3.85 times that of the control condition. And then the biosynthesis of ZnO NPs (7.59 g/L) was increased by 1.6 times. Furthermore, by using the Plackett-Burman design to improve the utilized biogenesis pathway, the biosynthesis of ZnO NPs (18.76 g/L) was increased by 4.3 times. To find the best growth production line, we used batch and fed batch fermentation modes to gradually scale up biomass output. All kinetics of studied cell growth were evaluated during fed-batch fermentation as follows: biomass yield was 271.45 g/L, yield coefficient was 94.25 g/g, and ZnO NPs yield was 345.32 g/L. In vitro, the effects of various dosages of the controllable biosynthetic ZnO NPs as antimicrobial and anticancer agents were also investigated. The treatments with controllable biosynthetic ZnO NPs had a significant impact on all the examined multidrug-resistant human pathogens as well as cancer cells.

Polyphenol-Rich Date Palm Fruit Seed (Phoenix Dactylifera L.) Extract Inhibits Labile Iron, Enzyme, and Cancer Cell Activities, and DNA and Protein Damage.

Date palm fruit seed (Phoenix dactylifera L.) extract (DSE), an under-utilized resource, is a rich source of polyphenols with high potency for disease prevention and antioxidative activities. For the first time, the present study demonstrated that DSE inhibits labile iron activity and DNA and BSA damage and inhibits acetylcholinesterase and tyrosinase activities. Moreover, DSE reduces the proliferation of hepatic, colorectal, and breast cancer cells dose-dependently through apoptotic mechanisms. Furthermore, DSE significantly suppressed the expression of both BCl-2 and P21 genes and increased the P53 expression level when compared with the untreated cells and the 5-FU treated cells. These findings suggest a strong potential for DSE in protecting against the iron-catalyzed ferroptosis that results in programmed cell death. The results also confirm the efficacy of DSE against cancer cells. Therefore, DSE constitutes a valuable candidate for developing functional foods and for natural compound-based chemotherapy for the pharmaceutical and nutraceutical industries.

Antibacterial activity of essential oils for combating colistin-resistant bacteria.

OBJECTIVES: Colistin (polymyxin E) is a bactericidal antibiotic used to treat severe infections caused by multidrug-resistant Gram-negative bacteria. The product of the mcr1 gene generates transferable plasmid-mediated colistin resistance, which has arisen as a worldwide health-care problem. This study aimed to isolate and identify colistin-resistant bacteria, and evaluate the ability of essential oils in its fights. METHODS: Twenty-seven bacterial isolates were collected from patients who were admitted to the National Cancer Institute, Cairo, Egypt, and processed using standard microbiological methods. Essential oils were purchased from AB Chem Company, Egypt, screened for antibacterial, cytotoxic activity, and (GC-MS) analysis. RESULTS: A total of 5 bacterial isolates were resistant to colistin with minimum inhibitory concentration (MIC) ranging from 6.25->200 µg/ml. Cinnamon oil exhibited the highest activity against colistin-resistant strains followed by thyme and eucalyptus oil. The (MIC) of cinnamon oils against resistant strains ranged from 4.88 to 312.5 µg/ml. Moreover, mcr-1 gene expression was extremely down-regulated after the treatment of bacterial strains with cinnamon oil and decreased to 20-35-fold. Examination of treated bacterial cells with sub-inhibitory concentrations under transmission electron microscopy showed various abnormalities occurred in most of these cells. CONCLUSIONS: Cinnamon oil exhibits antibacterial activity against colistin-resistant strains, showing it as a promising natural alternative in clinical therapy.

Grape seed proanthocyanidin extract inhibits DNA and protein damage and labile iron, enzyme, and cancer cell activities.

Grape seed extract from (Vitis vinifera) (VGSE) is an excellent source of various polyphenols that exhibit highly potent antioxidant and disease prevention properties. Although numerous biological activities, with potential for improving human health, have been reported for VGSE, there is a lack of data relating to the health benefits of VGSE on DNA damage, protein damage, labile iron activity, and enzyme inhibitory effects. This investigation demonstrated, for the first time, that VGSE inhibits DNA and BSA damage and labile iron activity in-vitro. Moreover, VGSE also inhibited in-vitro activities of AChE, tyrosinase, and α-amylase. VGSE treatment significantly reduced viability of MCF-7, Hep-G2, Caco-2, and Huh-7 cells after 48-h treatments. The results obtained provide additional support for the purported health benefits of VGSE and reinforce its potential in disease prevention and therapy, especially in relation to cancer.

Comparative Analysis of the Antiviral Activity of Camel, Bovine, and Human Lactoperoxidases Against Herpes Simplex Virus Type 1.

Lactoperoxidase is a milk hemoprotein that acts as a non-immunoglobulin protective protein and shows strong antimicrobial activity. Bovine milk contains about 15 and 7 times higher levels of lactoperoxidase than human colustrum and camel milk, respectively. Human, bovine, and camel lactoperoxidases (hLPO, bLPO, and cLPO, respectively) were purified as homogeneous samples with specific activities of 4.2, 61.3, and 8.7 u/mg, respectively. The optimal working pH was 7.5 (hLPO and bLPO) and 6.5 (cLPO), whereas the optimal working temperature for these proteins was 40 °C. The K m of hLPO, cLPO, and bLPO were 17, 16, and 19 mM, and their corresponding V max values were 2, 1.7, and 2.7 µmol/min ml. However, in the presence of H2O2, the K m values were 11 mM for hLPO and cLPO and 20 mM for bLPO, while the corresponding V max values were 1.17 for hLPO and 1.4 µmol/min ml for cLPO and bLPO. All three proteins were able to inhibit the herpes simplex virus type 1 (HSV-1) in Vero cell line model. The relative antiviral activities were proportional to the protein concentrations. The highest anti-HSV-1 activity was exhibited by bLPO that inhibited the HSV particles at a concentration of 0.5 mg/ml with the relative activity of 100%.

Screening the anti infectivity potentials of native N- and C-lobes derived from the camel lactoferrin against hepatitis C virus.

BACKGROUND: Hepatitis C virus (HCV) infection represents a worldwide health threat that still needs efficient protective vaccine and/or effective drug. The traditional medicine, such as camel milk, is heavily used by the large sector of HCV patients to control the infection due to the high cost of the available standard therapy. Camel milk contains lactoferrin, which plays an important and multifunctional role in innate immunity and specific host defense against microbial infection. Continuing the analysis of the effectiveness of camel lactoferrin against HCV, the current study aimed to separate and purify the native N- and C-lobes from the proteolytically cleaved camel lactoferrin (cLF) and to compare their in vitro activities against the HCV infection in Huh7.5 cells in order to determine the most active domain. METHODS: Lactoferrin and its digested N- and C-lobes were purified by Mono S 5/50 GL column and Superdex 200 5/150 column. The purified proteins were assessed through three venues: 1. To inhibit intracellular replication, HCV infected cells were treated with the proteins at different concentrations and time intervals; 2. The proteins were directly incubated with the viral particles (neutralization) and then such neutralized viruses were used to infect cells; 3. The cells were protected with proteins before exposure to the virus. The antiviral potentials of the cLf and its lobes were determined using three techniques: 1. RT-nested PCR, 2. Real-time PCR, and 3. Flow cytometry. RESULTS: N- and C-lobes were purified in two consecutive steps; using Mono-S and Superdex 200 columns. The molecular mass of N- and C-lobes was about 40 kDa. cLF and its lobes could prevent HCV entry into Huh 7.5 cells with activity reached 100% through direct interaction with the virus. The inhibition of intracellular viral replication by N-lobe is 2-fold and 3-fold more effective than that of the cLF and C-lobe, respectively. CONCLUSION: Generated native N- and C-lobes from camel lactoferrin demonstrated a range of noticeably different potentials against HCV cellular infectivity. The anti-HCV activities were sorted as N-lobe > cLf > C-lobe.

Examination of the activity of camel milk casein against hepatitis C virus (genotype-4a) and its apoptotic potential in hepatoma and hela cell lines.

BACKGROUND: Hepatitis C is a global health concern that represents a major cause of liver disease and socioeconomic burden. Currently, there is no vaccine that protects against this infection or drug that treats it effectively. The current treatment for hepatitis C virus (HCV) infection does not produce a sustained virologic response. Therefore,discovery and identification of a new drug for HCV treatment is a high priority.Camel milk is a traditional medicine that could improve the control of HCV. OBJECTIVES: To assess the potential effect of casein purified from camel milk on HCV cellular infectivity in a tissue culture model. MATERIALS AND METHODS: Casein was purified from defatted camel milk to electrophoretic homogeneity. PBMCs and HepG2 and HeLa cell lines were used. Three kinds of experiments were conducted. HCV was directly interacted with casein and then mixed with different cell types, casein was incubated with the cells and then exposed to HCV, and the HCV pre-infected cells were treated with casein at different concentrations and time intervals. Non-infected cells were used to assess cytotoxicity and the apoptosis effect of casein. RESULTS: Direct interaction of casein (with or without α-lactalbumin) with neither the virus nor the cells prevented HCV cell entry. However, casein with α-lactalbumin induced a cytotoxic effect in HepG2 and HeLa cell lines but not in human naïve leukocytes. At all concentrations tested, casein with α-lactalbumin could induce apoptosis in both infected and non-infected HepG2 cells. CONCLUSIONS: Camel milk casein (with or without α-lactalbumin) did not demonstrate any anti-HCV activity. However, the cellular apoptotic cascade was initiated in HepG2 and HeLa cells treated with casein (with α-lactalbumin) but not in naïve leukocytes.