Search

The use of cyclodextrins as carrier molecules is currently highly researched since they can improve not only the apparent water solubility and bioavailability of lipophilic drugs, but can also enhance stability or mask unpleasant tastes and smells. Artesunate is a naturally originated sesquiterpene derivative with great potential as an anticancer agent but poor water solubility. The aim of the present paper was the preparation, physicochemical characterization and biological activity assessment of three supramolecular adducts, namely guest–host inclusion complexes containing ATS as a guest molecule and randomly methylated-β-cyclodextrin (CD1), heptakis (2,6-di-O-methyl)-β-cyclodextrin (CD2) and heptakis (2,3,6-tri-O-methyl)-β-cyclodextrin (CD3), each of them used separately as hosts. The pure precursors and prepared complexes were analyzed using FTIR spectroscopy and thermal analysis, the formation of the adducts was simulated using molecular modeling and the MTT in vitro proliferation method was employed in order to evaluate their cytotoxicity on healthy (HaCaT) and pathologic (A375) skin cell lines. The instrumental techniques proved the results obtained from the molecular simulation and confirmed the formation of all three inclusion complexes. The biological activity evaluation revealed a dose-dependent cytotoxicity of ATS on the cancer cell line, effect that was diminished after complexation, but also a significantly reduced toxic effect on the healthy cells for the complexes when compared to that determined by pure ATS. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to determine the antioxidant capacity, the total phenol content, tannins, the cytotoxic and antiproliferative activity of some aqueous extracts obtained from spruce bark (Picea abies L.) and beech bark (Fagus sylvatica L.). In this regard, two types of extracts were obtained from both species using different methods of extraction: classical water bath extraction and ultrasound-assisted extraction. The antioxidant activity (AOA) was determined by means of DPPH assay and the cytotoxic and antiproliferative effects were determined using Alamar Blue technique and scratch assay. The total phenol content was determined colorimetrically by means of the Folin-Ciocalteu method. In vitro antitumor activity was tested on two different cell lines: A375 (human melanoma) and A549 (lung carcinoma) because of their different origin and metastatic potential. In addition, a non-tumor cell line (HaCaT human keratinocytes) was used in order to evaluate the samples selectivity. The results indicated that the aqueous extracts obtained by classical extraction had a higher antioxidant activity compared to the extracts obtained by ultrasound-assisted extraction. Moreover, the AOA of Picea abies L. bark extracts proved to be superior to those obtained from Fagus sylvatica L. bark extracts. Regarding the effect on cancer cells, the samples elicited a dose-dependent cytotoxic effect on A375 human melanoma cells, while on A549 lung carcinoma cells, the extractive solutions stimulated tumor cells viability, an effect that was reduced by increasing the concentration of the samples. Furthermore, the extractive solutions proved to possess antiproliferative properties when tested at the highest concentration; results that could be correlated with the antioxidant effects. In the case of the non-tumor cell line, the samples did not display a cytotoxic activity and stimulated cells proliferation. [ABSTRACT FROM AUTHOR]

Modulation of mitochondrial bioenergetics and glycolysis in malignancies has recently emerged a potential chemotherapeutic strategy since numerous malignant cells have overcome inhibition of the glycolytic pathway by increasing mitochondrial ATP production. Quercetin is a flavonoid with antioxidant, antiangiogenic, and chemoprotective properties but the mitochondrial effects are less characterized. The present study was purported to assess the effects of quercetin on the bioenergetic profile of B164A5 murine melanoma cell line. The oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) were measured at 24, 48, and 72 h of treatment of B164A5 murine melanoma cells with increasing concentrations (25, 50, 100, and 150 µM) of quercetin using the extracellular flux analyzer Seahorse XF24e (Seahorse Agilent). Analysis of mitochondrial function was performed in the presence of the classic modulators of the electron transport chain: oligomycin, FCCP, and rotenone. 72-h treatment with quercetin induced a dose-dependent decrease of all OCR parameters (basal respiration, proton leak, ATP turnover, maximal respiration, reserve capacity) as well as of ECAR. At variance, 48-h treatment induced a decrease of OCR and ECAR when quercetin was applied at 50, 100, and 150 µM, while the 24-h treatment induced a decrease of bioenergetic parameters only for the highest concentrations (100 and 150 µM) of the compound. Our data clearly demonstrated that quercetin elicited dose-dependent inhibitory effect on examined parameters of cellular bioenergetics that was most potent at 72 h of treatment. Thereby quercetin, modulating both glycolytic and mitochondrial pathways for ATP production, might be an efficient approach in killing cancer cells. [ABSTRACT FROM AUTHOR]

The original version of this article unfortunately contained a mistake. The equation was incorrectly presented. [ABSTRACT FROM AUTHOR]

Silver nanoparticles (AgNPs) are widely used in a variety of industrial and consumer applications and the disposal AgNP-containing materials is a potential source of environmental contamination. This study investigated the reaction of AgNPs with synthetic birnessite (δ-MnO2), a naturally-occurring MnO2 soil mineral shown in previous studies to oxidize both organic and inorganic dissolved species. The AgNPs used in this study ranged in size from 5 to 25 nm with an average particle diameter of 15.6 nm. Batch and kinetic reactions of MnO2-treated AgNP suspensions were studied by detecting AgNP oxidation to Ag+ using a combination of UV-Vis and microwave plasma atomic emission (MP-AES) spectrometries. Synchrotron K-edge X-ray absorption spectroscopy (XANES and EXAFS) was used to investigate the Ag oxidation state and structural characteristics of the reaction products. Oxidation of AgNP by MnO2 was detected in batch reactions showing an initial fast oxidation of AgNP to Ag+ (0–10 min) followed by a slower reaction (> 10 min) where Ag+ was removed by adsorption on MnO2 surfaces. XANES results confirmed that total AgNP oxidation by MnO2 occurred after 48 h when the Mn:Ag mole ratio treatment exceeded 5:1. The final AgNP oxidation product determined by EXAFS was Ag+ ion bound as a AgO4 tetrahedral structure in MnO2 interlayer cation exchange sites with Ag-O and Ag-Mn inter-atomic distances of 2.28 (± 0.02) and 3.88 (± 0.09) Å, respectively. This structure is in agreement with previous EXAFS studies of naturally-occurring Ag-bearing MnO2 mineral samples and represents one of many possible Ag+ binding sites on soil mineral surfaces. [ABSTRACT FROM AUTHOR]