Saponins from Medicago species display several biological activities, among them apoptotic effects against plant cells have been evidenced. In contrast, their cytotoxic and antitumor activity against ...animal cells have not been studied in great details.
To explore the cytotoxic properties of saponin from Medicago species against animal cells and their effect in combination with the antitumoral drug cisplatin.
Cytotoxic activity of saponin mixtures from M. arabica (tops and roots), M. arborea (tops) and M. sativa (tops, roots and seeds) and related prosapogenins from M. arborea and M. sativa (tops) against HeLa and MCF-7 cell lines is described. In addition, cytotoxicity of soyasaponin I and purified saponins (1-8) of hederagenin, medicagenic and zanhic acid is also presented. Combination experiments with cisplatin have been also conducted.
Saponins from M. arabica tops and roots (mainly monodesmosides of hederagenin and bayogenin) were the most effective to reduce proliferation of HeLa and MCF-7 cell lines. Among the purified saponins, the most cytotoxic was saponin 1, 3-O-ß-D-glucopyranosyl(1→2)-α-L-arabinopyranosyl hederagenin. When saponins, derived prosapogenins and pure saponins were used in combination with cisplatin, they all, to different extent, were able to potentiate cisplatin activity against HeLa cells but not against MCF-7 cell lines. Moreover uptake of cisplatin in these cell lines was significantly reduced.
Overall results showed that specific molecular types of saponins (hederagenin glycosides) have potential as anti-cancer agents or as leads for anti-cancer agents. Moreover saponins from Medicago species have evidenced interesting properties to mediate cisplatin effects in tumor cell lines.
By studying a model set of square‐planar Pt(NH3)aXbn (a + b = 4; Xb = combination of b halido ligands; n = 2 – b) complexes, we found that their δ(195Pt) NMR chemical shift decreases proportionally ...to the platinum bonded halido ligands' ionic radii overall sum. This confirms also for these systems, the already observed NMR shielding attributed to pseudo ring currents, circulating around the M–X bond axis. Moreover, the present data show that also the NH3 ligands are characterized by a constant NMR shielding ability toward the central metal. This could be rationalized in term of a “NMR effective molecular radius” of the NH3 ligand, affecting the observed δ(195Pt) as previously found for halido ligands. Interestingly, a δ(15N) decrease is observed in Pt bonded NH3 ligands if the ionic radius of a cis halido ligand is increased. The opposite occurs if the ionic radius of a trans halido ligand is increased. The two contrasting effects stem from both shielding electric ring currents affecting the cis ligands and prevailing trans‐influence due to coordinated halido ligands.
In the model Pt(NH3)3X+ (X = Cl, Br, I) complex the red torus and arrows represent the electric pseudo‐ring currents and the induced magnetic field, respectively, generated by an applied B° magnetic field. The considered Pt and cis to X N‐donors are indicated in red instead the trans is in blue. Different colors represent opposite NMR chemical shift variations (195Pt and 15N) observed when the X ligand both ionic radius and trans‐influence are varied. In this work, such considerations are extended to the general case of PtII complexes with X and NH3 ligands.
Heavy metals (HMs) are released into the environment by many human activities and persist in water even after remediation. The efficient filtration of solubilized HMs is extremely difficult. ...Phytoremediation appears a convenient tool to remove HMs from polluted water, but it is limited by the choice of plants able to adapt to filtration of polluted water in terms of space and physiological needs. Biomasses are often preferred. Aquatic moss biomasses, thanks to gametophyte characteristics, can act as live filtering material. The potential for phytoremediation of Hypnales aquatic mosses has been poorly investigated compared to aquatic macrophytes. Their potential is usually indicated as a tool for bioindication and environmental monitoring more than for pollutant removal. When phytoremediation has been considered, insufficient attention has been paid to the adaptability of biomasses to different needs. In this study the heavy metal uptake of moss
grown in two different light conditions, was tested with high concentrations of elements such as Pb, Cd, Zn, Cu, As, and Cr. This moss produces dense mats with few culture needs. The experimental design confirmed the capacity of the moss to accumulate HMs accordingly to their physiology and then demonstrated that a significant proportion of HMs was accumulated within a few hours. In addition to the biosorption effect, an evident contribution of the active simplistic mass can be evidenced. These reports of HM accumulation within short time intervals, show how this moss is particularly suitable as an adaptable bio-filter, representing a new opportunity for water eco-sustainable remediation.
Oleoylethanolamide (OEA) is a naturally occurring bioactive lipid belonging to the family of N-acylethanolamides. A variety of beneficial effects have been attributed to OEA, although the greater ...interest is due to its potential role in the treatment of obesity, fatty liver, and eating-related disorders. To better clarify the mechanism of the antiadipogenic effect of OEA in the liver, using a lipidomic study performed by
H-NMR, LC-MS/MS and thin-layer chromatography analyses we evaluated the whole lipid composition of rat liver, following a two-week daily treatment of OEA (10 mg kg
i.p.). We found that OEA induced a significant reduction in hepatic triacylglycerol (TAG) content and significant changes in sphingolipid composition and ceramidase activity. We associated the antiadipogenic effect of OEA to decreased activity and expression of key enzymes involved in fatty acid and TAG syntheses, such as acetyl-CoA carboxylase, fatty acid synthase, diacylglycerol acyltransferase, and stearoyl-CoA desaturase 1. Moreover, we found that both SREBP-1 and PPARγ protein expression were significantly reduced in the liver of OEA-treated rats. Our findings add significant and important insights into the molecular mechanism of OEA on hepatic adipogenesis, and suggest a possible link between the OEA-induced changes in sphingolipid metabolism and suppression of hepatic TAG level.
A smart nanocarrier system for cancer therapy, based on a recently developed technique for preparing pure nanometric calcium carbonate (CaCO3), was studied. Different approaches were used to obtain ...sustained release of cisplatin: at first, pure CaCO3 nanoparticles were evaluated as carriers, then the nanoparticles were functionalized with polymer or silanes, and finally they were employed as a substrate to build layer by layer (LbL) self-assembled polyelectrolyte nanocapsules. Loading efficiency and release kinetics were measured. The best loadings were obtained with the LbL nanocapsules, allowing for high loading efficiency and the possibility of controlling the release rate of the drug. The behavior of all the carriers was evaluated on four neoplastic cell lines, representative of different types of neoplastic disease, namely MCF-7 (breast cancer), SKOV-3 (ovarian cancer), HeLa (cervical cancer) and CACO-2 (human epithelial colorectal adenocarcinoma). Negligible cytotoxicity of the nanoparticles, functionalized nanoparticles, and nanocapsules was observed in experiments with all cell lines. Nanocapsules were functionalized with fluorescein isothiocyanate (FITC) in order to track their kinetic of internalization and localization in the cell line by confocal laser scanning microscopy (CLSM). The cytotoxicity of the loaded capsules was evaluated, showing cell survival rates close to those expected for non-encapsulated cisplatin at the same nominal concentration.
An efficient polymeric drug delivery system based on novel synthetic nanosized CaCO3 is reported that both efficiently loads the widespread anticancer drug cisplatin and controls its release. Optimal loading results were obtained with layer by layer self-assembled polyelectrolyte nanocapsules, which showed a cytotoxic activity comparable to free cisplatin. Display omitted
•Alginic acid/protamine (ALG/PRM) nanocapsules give loading efficiency and fast uptake.•The fastest uptake of nanocapsules is obtained for the human mammarian MCF-7 cell line.•Nanocapsules' intracellular localization is perinuclear for the four examined cell lines.•Loaded capsules have comparable cytotoxicity to free cisplatin at similar concentrations.
Cisplatin (cisPt), among the best known components of multi-drug front-line therapies used for the treatments of solid tumors, such as the childhood neuroblastoma, acts through DNA linking. ...Nevertheless, the cisPt effectiveness is compromised by the onset of severe side effects, including neurotoxicity that results in neurodegeneration, cell death, and drug-resistance. In the field of experimental oncology, aimed at overcoming cytotoxicity and chemoresistance, great efforts are devoted to the synthesis of new platinum-based drugs, such as Pt(O,O′-acac)(γ-acac)(DMS) (PtAcacDMS), which shows a specific reactivity with sulfur residues of enzymes involved in apoptosis. Autophagy, an evolutionary conserved degradation pathway for recycling of cytoplasmic components, represents one of the mechanisms adopted by cancer cells which contribute to drug-resistance. In the present study, standard acute (48 h-exposure) and long-term effects (7 day-recovery after treatment or 7 day-recovery followed by reseeding and 96 h-growth), of cisPt and PtAcacDMS (40 and 10 μM, respectively) were investigated in vitro employing rat B50 neuroblastoma as a cancer model. Using fluorescence and electron microscopy, as well as biochemical techniques, our data highlight a key role of the autophagic process in B50 cells. Specifically, long-term effects caused by cisPt lead to inhibition of the apoptotic process and paralleled by the activation of autophagy, thus evidencing that autophagy has a protective role after cisPt exposure, allowing cells to survive. Whereas, long-term effects produced by PtAcacDMS lead toward both apoptosis and autophagy activation. In conclusion, autophagy may represents an alternative cell death pathway, circumventing drug-resistance strategies employed by cancer cells to survive chemoterapy.
•Clinical use of cisPt limited by CNS severe side effects and drug-resistance•Synthesis of new PtAcacDMS to overcome cytotoxicity and chemoresistance•Autophagy role in B50 neuroblastoma cells after cisPt- and PtAcacDMS-exposure•PtAcacDMS as an alternative molecule in the treatment of cancer
Pomegranate peel extract is rich of interesting bioactive chemicals, principally phenolic compounds, which have shown antimicrobial, anticancer, and antioxidative properties. The aim of this work was ...to improve extract’ bioactivity through the adsorption on calcium carbonate nanocrystals. Nanocrystals revealed as efficient tools for extract adsorption reaching 50% of loading efficiency. Controlled release of the contained metabolites under acidic pH has been found, as it was confirmed by quantitative assay and qualitative study through NMR analysis. Specific functionality of inorganic nanocarriers could be also tuned by biopolymeric coating. The resulting coated nanoformulations showed a great antimicrobial activity against B. cinerea fungus preventing strawberries disease better than a commercial fungicide. Furthermore, nanoformulations demonstrated a good antiproliferative activity in neuroblastoma and breast cancer cells carrying out a higher cytotoxic effect respect to free extract, confirming a crucial role of nanocarriers. Finally, pomegranate peel extract showed a very high radical scavenging ability, equal to ascorbic acid. Antioxidant activity, measured also in intracellular environment, highlighted a protective action of extract-adsorbed nanocrystals twice than free extract, providing a possible application for new nutraceutical formulations.
In carbon and silicon tetrahalide compounds, the experimental 13C and 29Si NMR chemical‐shift values are known to increase or decrease on increasing the overall sum of the ionic radii of the bonded ...halides Σ(rh) (normal and inverse halogen dependence (NHD and IHD, respectively)). Herein, we extrapolate the main factors responsible for such NMR chemical shifts. Intriguingly, we found a characteristic value for the overall sum of the Pauling electronegativities of the bonded halides Σ(χh), which works as a triggering factor to determine the transition from the NHD to IHD. Below this Σ(χh) value, the chemical shift of the central atom was strictly related to only the Σ(rh) value, thus producing a NHD trend. Conversely, above this value, the chemical shift of the central atom was dependent on both the Σ(rh) and Σ(χh) values, thus producing a IHD trend. A simple model, in which the effect of the Σ(χh) value on 13C and 29Si NMR chemical shifts is related to an apparent increase in the Σ(rh) value, is deduced.
To clarify the relationship between the type of substituent bound to an atom and the observed frequencies of the NMR signals for its nucleus, we extrapolated the main factors responsible for the observed chemical shifts of the central atom in AX4 (A=C, Si; X4=combination of four halogen atoms; see figure) tetrahalide derivatives from experimental 13C and 29Si NMR chemical‐shift data.
In carbon and silicon tetrahalide compounds, the experimental
C and
Si NMR chemical-shift values are known to increase or decrease on increasing the overall sum of the ionic radii of the bonded ...halides Σ(r
) (normal and inverse halogen dependence (NHD and IHD, respectively)). Herein, we extrapolate the main factors responsible for such NMR chemical shifts. Intriguingly, we found a characteristic value for the overall sum of the Pauling electronegativities of the bonded halides Σ(χ
), which works as a triggering factor to determine the transition from the NHD to IHD. Below this Σ(χ
) value, the chemical shift of the central atom was strictly related to only the Σ(r
) value, thus producing a NHD trend. Conversely, above this value, the chemical shift of the central atom was dependent on both the Σ(r
) and Σ(χ
) values, thus producing a IHD trend. A simple model, in which the effect of the Σ(χ
) value on
C and
Si NMR chemical shifts is related to an apparent increase in the Σ(r
) value, is deduced.
Jellyfish as food represent a millennial tradition in Asia. Recently, jellyfish have also been proposed as a valuable source of protein in Western countries. To identify health risks associated with ...the potential human consumption of jellyfish as food, trace element accumulation was assessed in the gonads and umbrella tissues of the Mediterranean Rhizostoma pulmo (Macri, 1778), sampled over a period of 16 months along the shallow coastal waters a short distance from the city of Taranto, an area affected by metallurgic and oil refinery sources of pollution. Higher tissue concentrations of trace elements were usually detected in gonads than in umbrella tissue. In particular, significant differences in the toxic metalloid As, and in the metals Mn, Mo, and Zn, were observed among different tissues. The concentrations of vanadium were slightly higher in umbrella tissues than in gonads. No positive correlation was observed between element concentration and jellyfish size, suggesting the lack of bioaccumulation processes. Moreover, toxic element concentrations in R. pulmo were found below the threshold levels for human consumption allowed by Australian, USA, and EU Food Regulations. These results corroborate the hypothesis that R. pulmo is a safe, potentially novel food source, even when jellyfish are harvested from coastal areas affected by anthropogenic impacts.
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