Malformin-A1 (MA1) Sensitizes Chemoresistant Ovarian Cancer Cells to Cisplatin-Induced Apoptosis

High-grade epithelial ovarian cancer is a fatal disease in women frequently associated with drug resistance and poor outcomes. We previously demonstrated that a marine-derived compound MalforminA1 (MA1) was cytotoxic for the breast cancer cell line MCF-7. In this study, we aimed to examine the effect of MA1 on human ovarian cancer cells. The potential cytotoxicity of MA1was tested on cisplatin-sensitive (A2780S) and cisplatin-resistant (A2780CP) ovarian cancer cell lines using AlamarBlue assay, Hoechst dye, flow cytometry, Western blot, and RT-qPCR. MA1 had higher cytotoxic activity on A2780S (IC50 = 0.23 µM) and A2780CP (IC50 = 0.34 µM) cell lines when compared to cisplatin (IC50 = 31.4 µM and 76.9 µM, respectively). Flow cytometry analysis confirmed the cytotoxic effect of MA1. The synergistic effect of the two drugs was obvious, since only 13% of A2780S and 7% of A2780CP cells remained alive after 24 h of treatment with both MA1 and cisplatin. Moreover, we examined the expression of bcl2, p53, caspase3/9 genes at RNA and protein levels using RT-qPCR and Western blot, respectively, to figure out the cell death mechanism induced by MA1. A significant down-regulation in bcl2 and p53 genes was observed in treated cells compared to non-treated cells (p < 0.05), suggesting that MA1 may not follow the canonical pathway to induce apoptosis in ovarian cancer cell lines. MalforminA1 showed promising anticancer activity by inducing cytotoxicity in cisplatin-sensitive and cisplatin-resistant cancer cell lines. Interestingly, a synergistic effect was observed when MA1 was combined with cisplatin, leading to it overcoming its resistance to cisplatin.     

Computational Insights of Selective Intramolecular O-atom Transfer Mediated by Bioinspired Copper Complexes

The stereoselective copper-mediated hydroxylation of intramolecular C−H bonds from tridentate ligands is reinvestigated using DFT calculations. The computational study aims at deciphering the mechanism of C−H hydroxylation obtained after reaction of Cu(I) precursors with dioxygen, using ligands bearing either activated ( L¹ ) or non-activated ( L² ) C−H bonds. Configurational analysis allows rationalization of the experimentally observed regio- and stereoselectivity. The computed mechanism involves the formation of a side-on peroxide species ( P ) in equilibrium with the key intermediate bis-(μ-oxo) isomer ( O ) responsible for the C−H activation step. The P/O equilibrium yields the same activation barrier for the two complexes. However, the main difference between the two model complexes is observed during the C−H activation step, where the complex bearing the non-activated C−H bonds yields a higher energy barrier, accounting for the experimental lack of reactivity of this complex under those conditions.     

Algorithme de Neumann–Dirichlet pour des problèmes de contact unilatéral : Résultat de convergenceNeumann–Dirichlet algorithm for unilateral contact problems: Convergence results

In this Note, we propose and we prove the convergence of a Neumann–Dirichlet algorithm in order to approximate a Signorini problem between two elastic bodies. The idea is to retain the natural interface between the two bodies as numerical interface for the domain decomposition and to replace the Dirichlet problem in [4] by a variational inequality. To cite this article: G. Bayada et al., C. R. Acad. Sci. Paris, Ser. I 335 (2002) 381–386.     

Carboxybetaine methacrylate polymers offer robust, long-term protection against cell adhesion

Films of poly(carboxybetaine methacrylate), poly(CBMA), grafted onto microetched gold slides are effective in preventing nonspecific adhesion of cells of different types. The degree of adhesion resistance is comparable to that achieved with the self-assembled monolayers, SAMs, of oligo(ethylene glycol) alkanethiolates. In sharp contrast to the SAMs, however, substrates protected with poly(CBMA) can be stored in dry state without losing their protective properties for periods up to 2 weeks.     

Phase equilibria of mixed carbon dioxide and tetrahydrofuran hydrates in sodium chloride aqueous solutions

In this work, the competing effects of sodium chloride (NaCl) and tetrahydrofuran (THF) on carbon dioxide hydrate formation are investigated through phase equilibrium measurements. The phase behaviour in the hydrate forming region for the binary system carbon dioxide–water, the ternary systems carbon dioxide–tetrahydrofuran–water and ternary carbon dioxide–sodium chloride–water and, in addition, the quaternary system carbon dioxide–tetrahydrofuran–water–sodium chloride are determined experimentally, using a Cailletet apparatus. All measurements are made in a temperature and pressure region of 275–290 K and 0.5–7.0 MPa, respectively. In these ranges, three different hydrate equilibrium curves are measured namely: H-L_W-V, H-L_W-L_V-V and H-L_W-L_V. The formation of an organic-rich liquid phase in the systems due to a liquid–liquid two-phase split between water and tetrahydrofuran when pressurized with carbon dioxide causes the occurrence of an upper quadruple point (Q₂) to evolve into a four-phase H-L_W-L_V-V equilibrium line. The presence of sodium chloride in the quaternary system enhances the split between the two liquids due to the salting-out effect. It was found that the hydrate promoting effect of tetrahydrofuran is able to suppress the inhibiting effect of sodium chloride especially at lower concentration of sodium chloride.     

Identification of a copper(I) intermediate in the conversion of 1-aminocyclopropane carboxylic acid (ACC) into ethylene by Cu(II)-ACC complexes and hydrogen peroxide

Several Cu(II) complexes with ACC (=1-aminocyclopropane carboxylic acid) or AIB (=aminoisobutyric acid) were prepared using 2,2'-bipyridine, 1,10-phenanthroline, and 2-picolylamine ligands: [Cu(2,2'-bipyridine)(ACC)(H2O)](ClO4) (1a), [Cu(1,10-phenanthroline)(ACC)](ClO4) (2a), [Cu(2-picolylamine)(ACC)](ClO4) (3a), and [Cu(2,2'-bipyridine)(AIB)(H2O)](ClO4) (1b). All of the complexes were characterized by X-ray diffraction analysis. The Cu(II)-ACC complexes are able to convert the bound ACC moiety into ethylene in the presence of hydrogen peroxide, in an "ACC-oxidase-like" activity. A few equivalents of base are necessary to deprotonate H2O2 for optimum activity. The presence of dioxygen lowers the yield of ACC conversion into ethylene by the copper(II) complexes. During the course of the reaction of Cu(II)-ACC complexes with H2O2, brown species (EPR silent and lambda max approximately 435 nm) were detected and characterized as being the Cu(I)-ACC complexes that are obtained upon reduction of the corresponding Cu(II) complexes by the deprotonated form of hydrogen peroxide. The geometry of the Cu(I) species was optimized by DFT calculations that reveal a change from square-planar to tetrahedral geometry upon reduction of the copper ion, in accordance with the observed nonreversibility of the redox process. In situ prepared Cu(I)-ACC complexes were also reacted with hydrogen peroxide, and a high level of ethylene formation was obtained. We propose Cu(I)-OOH as a possible active species for the conversion of ACC into ethylene, the structure of which was examined by DFT calculation.     

ACC-Oxidase like activity of a copper (II)-ACC complex in the presence of hydrogen peroxide. Detection of a reaction intermediate at low temperature

A Cu(II)-ACC complex [(Bpy)Cu(ACC)(H2O)]ClO4 (1) was prepared and its treatment with hydrogen peroxide gave rise to ethylene production in an ACC-Oxidase like activity. A brown species that could be a key intermediate in the reaction was detected at low temperature.     

Experimental observations on the competing effect of tetrahydrofuran and an electrolyte and the strength of hydrate inhibition among metal halides in mixed CO2 hydrate equilibria

In the present work, experimental data on the equilibrium conditions of mixed CO₂ and THF hydrates in aqueous electrolyte solutions are reported. Seven different electrolytes (metal halides) were used in this work namely sodium chloride (NaCl), calcium chloride (CaCl₂), magnesium chloride (MgCl₂), potassium bromide (KBr), sodium fluoride (NaF), potassium chloride (KCl), and sodium bromide (NaBr). All equilibrium data were measured by using Cailletet apparatus. Throughout this work, the overall concentration of CO₂ and THF were kept constant at (0.04 and 0.05) mol fraction, respectively, while the concentration of electrolytes were varied. The experimental temperature ranged from (275 to 305) K and pressure up 7.10 MPa had been applied. From the experimental results, it is concluded that THF, which is soluble in water is able to suppress the salt inhibiting effect in the range studied. In all quaternary systems studied, a four-phase hydrate equilibrium line was observed where hydrate (H), liquid water (L_W), liquid organic (L_V), and vapour (V) exist simultaneously at specific pressure and temperature. The formation of this four-phase equilibrium line is mainly due to a liquid–liquid phase split of (water + THF) mixture when pressurized with CO₂ and the split is enhanced by the salting-out effect of the electrolytes in the quaternary system. The strength of hydrate inhibition effect among the electrolytes was compared. The results shows the hydrate inhibiting effect of the metal halides is increasing in the order NaF < KBr < NaCl < NaBr < CaCl₂ < MgCl₂. Among the cations studied, the strength of hydrate inhibition increases in the following order: K⁺ < Na⁺ < Ca²⁺ < Mg²⁺. Meanwhile, the strength of hydrate inhibition among the halogen anion studied decreases in the following order: Br^? > Cl^? > F^?. Based on the results, it is suggested that the probability of formation and the strength of ionic–hydrogen bond between an ion and water molecule and the effects of this bond on the ambient water network are the major factors that contribute to hydrate inhibition by electrolytes.