Quick: An exogenously induced quick increase of the H2S concentration (80 s) in MCF‐7 cells can be visualized by ratiometric imaging using a new probe (CouMC) that can target mitochondria. CouMC was constructed by combining merocyanine and coumarin fluorophores. The selective nucleophilic addition of HS− to the merocyanine derivative at neutral pH is crucial for the rapid H2S detection.
Cancer cells usually adapt metabolic phenotypes to chemotherapeutics.Adefensive strategy against this flexibility is to modulate signaling pathwaysr elevant to cancer bioenergetics.Atriphenylphosphonium-modified terpyridine platinum(II) complex (TTP) was designed to inhibit thioredoxin reductase (TrxR) and multiple metabolisms of cancer cells. TTP exhibited enhanced cytotoxicity against cisplatin-insensitive human ovarian cancer cells in ac aspase-3-independent manner and showed preferential inhibition to mitochondrial TrxR. The morphology and function of mitochondria were severely damaged, and the levels of mitochondrial and cellular reactive oxygen species were decreased. As ar esult, TTP exerted strong inhibition to both mitochondrial and glycolytic bioenergetics,t hus inducing cancer cells to enter ah ypometabolic state.
The aggregation of amyloid beta-peptide (Abeta) in plaques in brain tissue is highly associated with Alzheimer's disease (AD). Aberrant homeostasis of cerebral metals such as Zn(2+) and Cu(2+) may facilitate the formation of the pathogenetic amyloid plaques. Further, the accumulation of redox-active Cu(2+) in these plaques leads to the generation of reactive oxygen species, which mediates the conspicuous oxidative damage to the brain in AD. In this study, the effect of macrocyclic polyamine chelators, cyclen and cyclam, on the aggregation of Abeta40 induced by Zn(2+) or Cu(2+) was investigated using turbidometry, thioflavin T fluorescence spectroscopy, electrospray ionization mass spectrometry, inductively coupled plasma mass spectrometry, BCA protein assay, circular dichroism spectroscopy, and atomic force microscopy. The solubility of Zn(2+)- or Cu(2+)-induced Abeta40 aggregates is greatly increased by cyclen or cyclam as compared to that without chelators, and the solubilization is not affected by other essential metal ions such as Ca(2+) and Mg(2+). Moreover, the metal-induced beta-sheet structure of Abeta40 can be reconverted to its original random coil conformation, and the generation of H(2)O(2) mediated by the Cu-Abeta40 complex can also be inhibited by these chelators. Preliminary tests on neuronal cells indicate that these chelators are capable of reducing the toxicity of metal-Abeta40 aggregates. These observations suggest that cyclen and cyclam could be lead compounds as neuroprotective or neurorescue agents for the treatment of AD.
Schnell: Mithilfe einer neuen Sonde, die Mitochondrien markieren kann, lässt sich ein von außen induzierter, schneller Anstieg der H2S‐Konzentration (80 s) in MCF‐7‐Zellen durch ratiometrische Bildgebung visualisieren. Die selektive nukleophile Addition von HS− an das Merocyaninderivat bei neutralem pH‐Wert ist entscheidend für die schnelle H2S‐Detektion.
To develop a novel type of semi-IPN particles using biocompatible materials, hydroxypropylcellulose-poly(acrylic acid) (HPC-PAA) particles with semi-interpenetrating polymer network structure and a porosity-structural surface were prepared by direct polymerization of acrylic acid monomer in the reaction system comprised of HPC and AA monomer and N,N'-methylenebisacrylamide (MBAAm). The properties of HPC-PAA gel particles were characterized by dynamic light scattering, FT-IR, transmission electron microscopy, and atomic force microscope. It is found that the formation of HPC-PAA gel particles is driven by the hydrogen bonding interaction between proton-donating PAA and proton-accepting HPC. These HPC-PAA gel particles exhibit thermo and pH dual-responsive behaviors. Depending on the chemical composition and the degree of cross-linking, the thermo-responsive property of HPC-PAA gel particles can be shifted from the UCST to the LCST property, and particle sizes can be changed from 100 to 1 microm in a controllable way. Successful loading of the gel particles with oxaliplatin, a hydrophilic antitumor drug, was achieved by take advantage of the complex interaction between the platinum atom of oxaliplatin and the carboxylic group of PAA in the gel particles. In vitro cytotoxicity assay indicates that the oxalipatin-loaded HPC-PAA gel particles have high anticancer activity. Considering the good biosafety, simple and mild preparation strategy and tunable size as well as the stimuli-responsive properties, the HPC-PAA gel particles should be a promising candidate for the drug delivery system.
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