Ethanolic extract of propolis (EEP) is one of the richest sources of phenolic acids and flavonoids. EEP and its phenolic compounds have been known for various biological activities including ...immunopotentiation, chemopreventive and antitumor effects. Tumor necrosis factor related apoptosis inducing ligand (TRAIL) is a naturally occurring anticancer agent that preferentially induces apoptosis in cancer cells and is not toxic toward normal cells. We examined the cytotoxic and apoptotic effect of EEP and phenolic compounds identified in propolis in combination with TRAIL on HeLa cancer cells. HeLa cells were resistant to TRAIL-induced apoptosis. Our study demonstrated that EEP and its components significantly sensitize to TRAIL induced death in cancer cells. The percentage of the apoptotic cell after exposure to 50 microg/mL EEP and 100 ng/mL TRAIL increased to 71.10 +/- 1.16%. The strongest cytotoxic effect in combination with TRAIL on HeLa cells exhibited apigenin and CAPE at the concentration of 50 microM (58.87 +/- 0.75% and 49.59 +/- 0.39%, respectively). In this report, we show for the first time that EEP markedly augmented TRAIL mediated apoptosis in cancer cells and confirmed the importance of propolis in chemoprevention of malignant tumors.
New trehalose-containing hydrogels and the first hydrogels cross-linked by mono- or disaccharide acetals that are degradable in acidic medium were designed and synthesized. The cross-linking agent ...was obtained in acetalization reaction of trehalose with x-allyloxybenzaldehyde in which diallyl compounds were formed and used afterward in free radical copolymerization with N-isopropylacrylamide (NIPAAm) to provide thermo-sensitive hydrogels. Depending on the trehalose diacetal isomer and solvent system used in copolymerization, as well the degree of network cross-linking, these hydrogels differed in morphology, swelling and deswelling behavior and time of degradation. Compared with conventional PNIPAAm hydrogels they are degradable what makes them good materials for biomedical applications.
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•Thermo-sensitive hydrogels cross-linked by trehalose diacetals were synthesized.•Trehalose diacetal cross-linker provide acid-degradability to hydrogels.•Hydrogels differed in morphology swelling ratio and degradation time were obtained.
Colon cancer is one of the leading causes of death in the world. The search for effective and minimally invasive methods of treating colon cancer is the aim of modern medicine. Chalcones and their ...derivatives have shown an anticancer activity. The aim of the study was to evaluate the effect of methoxy-derivatives of 2’-hydroxychalcones: 2’-hydroxy-3”-methoxychalcone (TJ3), 2’-hydroxy-2”-methoxychalcone (TJ6) and 2’-hydroxy-4”-metoxychalcone (TJ7) at the concentrations of 10 µM and 25 µM on the release of IL-8, MIF, VCAM-1, ICAM-1 by colon cancer SW480 and SW620 cell lines. The cytokines and adhesion molecules were detected using the Bio-Plex Magnetic Luminex Assay and the Bio-Plex Suspension Array System. Our results showed that all tested methoxy-derivatives of 2’-hydroxychalcone compounds significantly reduced ICAM-1 released by SW480 cancer cells. The tested compounds at both concentrations did not significantly affect VCAM-1 released by SW480 and SW620 cancer cell lines. All methoxy-derivatives significantly reduced the concentration of MIF in dose dependent manner on SW480 cells. The TJ3 at the concentration of 25 µM significantly decreased IL-8 secreted by SW480 and SW620 cancer cells. Our results demonstrated that tested methoxy-derivatives of 2’-hydroxychalcones showed modulating effect on colon cancer cells.
•The tested compounds could modulating selected mediators released by colon cancer cells.•The soluble factors such as cytokines or adhesion molecules secreted by colon cancer cells determine the microenvironment in which tumor develops.•The tested compounds can be used in cancer chemoprevention through indirect effect in the tumor microenvironment.
The extension of human life makes it more and more important to prevent and treat diseases of the elderly, including Alzheimer's disease (AD) and osteoporosis. Little is known about the effects of ...drugs used in the treatment of AD on the musculoskeletal system. The aim of the present study was to investigate the effects of donepezil, an acetylcholinesterase inhibitor, on the musculoskeletal system in rats with normal and reduced estrogen levels. The study was carried out on four groups of mature female rats: non-ovariectomized (NOVX) control rats, NOVX rats treated with donepezil, ovariectomized (OVX) control rats and OVX rats treated with donepezil. Donepezil (1 mg/kg p.o.) was administered for four weeks, starting one week after the ovariectomy. The serum concentrations of CTX-I, osteocalcin and other biochemical parameters, bone mass, density, mineralization, histomorphometric parameters and mechanical properties, and skeletal muscle mass and strength were examined. Estrogen deficiency increased bone resorption and formation and worsened cancellous bone mechanical properties and histomorphometric parameters. In NOVX rats, donepezil decreased bone volume to tissue volume ratio in the distal femoral metaphysis, increased the serum phosphorus concentration and tended to decrease skeletal muscle strength. No significant bone effects of donepezil were observed in OVX rats. The results of the present study indicate slightly unfavorable effects of donepezil on the musculoskeletal system in rats with normal estrogen levels.
Memantine is an N-methyl-D-aspartate (NMDA) receptor antagonist used in the treatment of Alzheimer's disease (AD). NMDA receptors are expressed on bone cells. The aim of the present study was to ...investigate the effects of memantine on the rat musculoskeletal system. Taking into account that most of female AD patients are postmenopausal, the study was carried out on intact and ovariectomized (estrogen-deficient) rats. Mature Wistar rats were divided into following groups: non-ovariectomized (NOVX) control rats, NOVX rats treated with memantine, ovariectomized (OVX) control rats, and OVX rats treated with memantine. Memantine (2 mg/kg p.o.) was administered once daily for four weeks, starting one week after ovariectomy. The serum bone turnover marker and cytokine levels, bone density, mass, mineralization, mechanical properties, histomorphometric parameters of compact and cancellous bone, skeletal muscle mass and grip strength were determined. In NOVX rats, memantine slightly decreased the strength of compact bone of the femoral diaphysis (parameters in the yield point) and unfavorably affected histomorphometric parameters of cancellous bone (the femoral epiphysis and metaphysis). In OVX rats, in which estrogen deficiency induced osteoporotic changes, memantine increased the phosphorus content in the femoral bone mineral. No other effects on bone were observed in the memantine-treated OVX rats. In conclusion, the results of the present study indicated slight damaging skeletal effects of memantine in rats with normal estrogen levels.
•Memantine unfavorably affected bones in rats with normal estrogen levels.•Memantine slightly worsened cancellous bone microstructure and compact bone strength.•Memantine did not affect most of bone parameters in estrogen-deficient rats.•The results indicate the possibility of adverse skeletal effects of memantine.
Coumarins are a very common type of secondary plant metabolites with a broad spectrum of biological activities. Psoralidin is a naturally occurring furanocoumarin isolated from Psoralea corylifolia ...possessing anticancer and chemopreventive properties. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in cancer cells with no toxicity toward normal tissues. Endogenous TRAIL plays an important role in immune surveillance and defence against cancer cells. Coumarins can modulate TRAIL-mediated apoptosis in cancer cells. We examined the cytotoxic and apoptotic activities of psoralidin in combination with TRAIL on HeLa cancer cells. The cytotoxicity was measured by MTT and LDH assays. The apoptosis was detected using annexin V-FITC staining and mitochondrial membrane potential was evaluated using DePsipher staining by fluorescence microscopy. Death receptor (TRAIL-R1/DR4 and TRAIL-R2/DR5) expression was analyzed using flow cytometry. Psoralidin enhanced TRAIL-induced apoptosis in HeLa cells through increased expression of TRAIL-R2 death receptor and depolarization of mitochondrial membrane potential. Our study indicated that psoralidin augmented the anticancer effects of TRAIL and confirmed a potential use of coumarins in cancer chemoprevention.
Chemokines, also known as chemotactic cytokines, stimulate the migration of immune cells. These molecules play a key role in the pathogenesis of inflammation leading to atherosclerosis, ...neurodegenerative disorders, rheumatoid arthritis, insulin-resistant diabetes, and cancer. Moreover, they take part in inflammatory bowel disease (IBD). The main objective of our research was to determine the activity of methyl-derivatives of flavanone, namely, 2'-methylflavanone (
), 3'-methylflavanone (
), 4'-methylflavanone (
), and 6-methylflavanone (
), on the releasing of selected cytokines by RAW264.7 macrophages activated by LPS. We determined the concentration of chemokines belonging to the CC chemokine family, namely, MCP-1, MIP-1β, RANTES, and eotaxin, using the Bio-Plex Magnetic Luminex Assay and the Bio-PlexTM 200 System. Among the tested compounds, only
and
had the strongest effect on inhibiting the examined chemokines' release by macrophages. Therefore,
and
appear to be potentially useful in the prevention of diseases associated with the inflammatory process.
The burden of cardiovascular disease and the percentage of frail patients in the aging population will increase. This study aims to assess the circulating levels of several cytokines in frail ...patients. This is an ancillary analysis of the FRAPICA trial. The ratio of men/women changed from robust through frail groups from 3:1 to 1:2. The groups are comparable in terms of age and body measurements analysis (weight, height, and BMI), yet the frail patients have significantly reduced fat-free mass, and more often have been diagnosed with diabetes. Frail patients have higher fibroblast growth factor basic (FGF basic) and follistatin levels (borderline significance). In multiple linear regression modeling of fat-free mass, we identified FGF basic, osteopontin, stem cell factor, soluble suppression of tumorigenicity 2, soluble epidermal growth factor receptor, soluble human epidermal growth factor receptor 2, follistatin, prolactin, soluble interleukin 6 receptor alfa, platelet endothelial cell adhesion molecule 1, soluble vascular endothelial cell growth factor receptor 1, leptin, soluble angiopoietin/tyrosine kinase 2, and granulocyte colony-stimulating factor. We have identified a few cytokines that correlate with fat-free mass, a hallmark of frailty. They comprise the kinins implicated in bone and muscle metabolism, fibrosis, vascular wall function, inflammation, endocrine function, or regulation of bone marrow integrity.
Propolis, owing to its antibacterial and anti-inflammatory properties, acts as a cariostatic agent, capable of preventing the accumulation of dental plaque and inhibiting inflammation. The ...anti-inflammatory properties of propolis are attributed to caffeic acid phenethyl ester (CAPE), which is present in European propolis. The objective of the conducted study was to assess the anti-inflammatory effects of the Polish ethanolic extract of propolis (EEP) and isolated CAPE on stimulated with LPS and IFN-α, as well as the combination of LPS and IFN-α. The cytotoxicity of the tested compounds was determined using the MTT assay. The concentrations of specific cytokines released by the HGF-1 cell line following treatment with EEP (25–50 µg/mL) or CAPE (25–50 µg/mL) were assessed in the culture supernatant. In the tested concentrations, both CAPE and EEP did not exert cytotoxic effects. Our results demonstrate that CAPE reduces TNF-α and IL-6 in contrast to EEP. Propolis seems effective in stimulating HGF-1 to release IL-6 and IL-8. A statistically significant difference was observed for IL-8 in HGF-1 stimulated by LPS+IFN-α and treated EEP at a concentration of 50 µg/mL (p = 0.021201). Moreover, we observed that CAPE demonstrates a stronger interaction with IL-8 compared to EEP, especially when CAPE was administered at a concentration of 50 µg/mL after LPS + IFN-α stimulation (p = 0.0005). Analysis of the phenolic profile performed by high-performance liquid chromatography allowed identification and quantification in the EEP sample of six phenolic acids, five flavonoids, and one aromatic ester—CAPE. Propolis and its compound—CAPE—exhibit immunomodulatory properties that influence the inflammatory process. Further studies may contribute to explaining the immunomodulatory action of EEP and CAPE and bring comprehensive conclusions.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in cancer cells without toxicity to normal cells. TRAIL binds to death receptors, TRAIL-R1 (DR4) and TRAIL-R2 (DR5) ...expressed on cancer cell surface and activates apoptotic pathways. Endogenous TRAIL plays an important role in immune surveillance and defense against cancer cells. However, as more tumor cells are reported to be resistant to TRAIL mediated death, it is important to search for and develop new strategies to overcome this resistance. Chalcones can sensitize cancer cells to TRAIL-induced apoptosis. We examined the cytotoxic and apoptotic effects of TRAIL in combination with four chalcones: chalcone, isobavachalcone, licochalcone A and xanthohumol on HeLa cancer cells. The cytotoxicity was measured by MTT and LDH assays. The apoptosis was detected using annexin V-FITC staining by flow cytometry and fluorescence microscopy. Death receptor expression was analyzed using flow cytometry. The decreased expression of death receptors in cancer cells may be the cause of TRAIL-resistance. Chalcones enhance TRAIL-induced apoptosis in HeLa cells through increased expression of TRAIL-R2. Our study has indicated that chalcones augment the antitumor activity of TRAIL and confirm their cancer chemopreventive properties.
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