RESUMO
Some hydroxamate compounds induce cancer cell death by intracellular reactive oxygen species (ROS). This study introduced the hydroxamate core into lovastatin, a fungus metabolite clinically used for the treatment of hypercholesterolemia. The resulting compounds were evaluated for the activity for inducing ROS production. Most compounds exhibited higher activity than original lovastatin. Of these compounds, compound 3c had the most potent activity. Test of cytotoxicity in a panel of human cancer cell lines indicated compound 3c had activities superior to cisplatin in prostate cancer PC-3 cells and breast cancer T47D cells. In contrast, it in amounts up to 40µM had a much lower cytotoxic effect on normal human IMR-90 cells. Further profiling of cell cycle progression, cell apoptosis, and DNA damage activated checkpoint signaling pathway revealed the important role of compound 3c-mediated cytotoxicity in ROS generation.
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Ácidos Hidroxâmicos/química , Ácidos Hidroxâmicos/farmacologia , Lovastatina/análogos & derivados , Lovastatina/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Anticolesterolemiantes/química , Anticolesterolemiantes/farmacologia , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismoRESUMO
Quinone methides (QMs) are very important intermediates in chemistry. These species are most often generated in situ with metal oxidants and transition metal complexes. Here, tip-enhanced Raman spectroscopy (TERS) has been implemented to investigate the in situ oxidative generation of a QM species from alkylphenols facilitated by a transition metal complex. Using TERS, the metal oxidant-mediated transformation of a phenol species has been observed. The subsequent oxidative addition reaction of QM has also been identified based on distinct vibrational features, which have been assigned based on density functional theory (DFT). This study may establish TERS as a chemical detection tool for various QM-mediated reactions.
Assuntos
Indolquinonas/química , Análise Espectral Raman/métodos , Linhagem Celular Tumoral , Teoria da Densidade Funcional , Humanos , OxirreduçãoRESUMO
The detection of carbohydrates in human body fluids is critical for disease diagnosis and healthy monitoring. Despite recent advances in glucose sensing, multiplex detection of different carbohydrates within a single assay that is capable of efficiently providing richer health information remains challenging. Herein, we report a versatile surface-enhanced Raman spectroscopy-based platform for the quantitative detection of monosaccharides (glucose, fructose, and galactose) in one test using a displace-and-trap mechanism. Moreover, due to the use of multiple optical interference-free (1800-2200 cm-1) signal-independent Raman probes, the detection range of this platform (0.125-7 mg/dL) perfectly covers physiological concentrations, enabling the quantitative detection of glucose and galactose in clinical human saliva samples. This work provides a noninvasive and high-efficiency potential tool for the screening of clinical diabetes and other carbohydrate-related diseases.
Assuntos
Saliva , Análise Espectral Raman , Carboidratos , Frutose , Glucose , HumanosRESUMO
The limited availability of nasopharyngeal carcinoma-related progression biomarker array kits that offer physicians comprehensive information is disadvantageous for monitoring cancer progression. To develop a biomarker array kit, systematic identification and differentiation of a large number of distinct molecular surface-enhanced Raman scattering (SERS) reporters with high spectral temporal resolution is a major challenge. To address this unmet need, we use the chemistry of metal carbonyls to construct a series of unique SERS reporters with the potential to provide logical and highly multiplex information during testing. In this study, we report that geometric control over metal carbonyls on nanotags can produce 14 distinct barcodes that can be decoded unambiguously using commercial Raman spectroscopy. These metal carbonyl nanobarcodes are tested on human blood samples and show strong sensitivity (0.07 ng/mL limit of detection, average CV of 6.1% and >92% degree of recovery) and multiplexing capabilities for MMPs.
Assuntos
Técnicas Biossensoriais/métodos , Carcinoma Nasofaríngeo/diagnóstico , Neoplasias Nasofaríngeas/diagnóstico , Análise Espectral Raman , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/química , Progressão da Doença , Metaloproteinases da Matriz/sangue , Metaloproteinases da Matriz/química , Nanopartículas Metálicas/química , Nanogéis/química , Carcinoma Nasofaríngeo/sangue , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/sangue , Neoplasias Nasofaríngeas/patologia , Compostos Organometálicos/química , Sensibilidade e Especificidade , Propriedades de SuperfícieRESUMO
Detection of chemical reactions in living cells is critical in understanding physiological metabolic processes in the context of nanomedicine. Carbon monoxide (CO) is one of the important gaseous signaling molecules. Surface-enhanced Raman spectroscopy (SERS)-based CO-releasing nanoparticles (CORN) is utilized to investigate the chemical reaction of CO delivery in live cells. Using SERS CORN, carbonyl dissociation from CORN-Ag-CpW(CO)3 to CORN-Ag-CpW(CO)2 in live cells is observed. The subsequent irreversible degradation to CO-free CORN is a consequence of oxidative stress in cells. This observation affirms the step transition of CORN-Ag-CpW(CO)3 in cellular: CORN-Ag-CpW(CO)3 first proceeds via a direct loss of one CO followed by a oxidative decomposition giving rise to CORN-Ag-WO3 and as well as the release of one equivalents of CO. Importantly, the decarbonylation process can be correlated with the level of inflammatory biomarkers. For the first time, we provide unambiguous evidence for the steps transition of CO-release mechanism in cellular.
Assuntos
Monóxido de Carbono/metabolismo , Nanopartículas Metálicas/administração & dosagem , Prata/administração & dosagem , Tungstênio/administração & dosagem , Animais , Linhagem Celular , Citocinas/metabolismo , Humanos , Camundongos , Análise Espectral RamanRESUMO
A novel trinuclear complex [Ni3(µ3-dbay)4Cl2]I3 (1) with a mixed-valence state was prepared by reacting the tridentate ligand 1,13,14-triaza-dibenz[a,j]anthracene (dibenzanthyridine = dbay) with anhydrous NiCl2 and sodium tetraphenylborate. The title compound provides the first example of a trinuclear nickel-anthyridine-based string complex in which the metal framework of complex 1 consists of NiII-NiI-NiII. X-ray crystallography, magnetic susceptibility and detailed EPR measurements were performed to characterize the structure and magnetic properties of this unique complex.
RESUMO
AIMS: Alterations in histone proteins can lead to breast tumorigenesis. Selective histone deacetylase 8 (HDAC8) inhibitors with fewer adverse effects have been developed. A more comprehensive study of alterations and its mechanisms in HDAC8 is required. In this study, we investigated mechanisms of dysregulation of HDAC8 expression and its biological role and pathways in breast cancer. MAIN METHODS: Alterations in HDAC8 were analyzed in Taiwanese breast cancer patients; and in tissue samples from The Cancer Genome Atlas (TCGA) data set that were derived from Western countries. Knockdown by si-HDAC8, treatment with the HDAC8-specific inhibitor PCI-34051, SRB assays, wound healing, Transwell migration assays, Illumina BeadArray™ arrays and Ingenuity Pathway Analysis (IPA) were performed in breast cancer cells. KEY FINDINGS: HDAC8 mRNA expression was upregulated in paired breast cancer tissue from Taiwanese patients and in paired breast cancer tissues from the TCGA data set. Hypomethylation of promoter regions was significantly correlated with HDAC8 mRNA overexpression in 588 breast cancer patients from the TCGA data set and was associated with poor prognosis in early-stage breast cancer. HDAC8 mRNA overexpression was associated with late stages and tumor progression. Wound healing and Transwell migration assays revealed that knockdown by si-HDAC8 or PCI-34051 treatment significantly inhibited breast cancer cell migration. Knockdown by si-HDAC8, Illumina BeadArray™ arrays and IPA found that ID3 and PTP4A2 pathways were regulated by HDAC8 in cancer cell migration. SIGNIFICANCE: Hypomethylation of the HDAC8 promoter is correlated with HDAC8 overexpression and breast cancer progression and is a potential prognosis marker and drug target.