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Synthesis and Anticancer Properties of Water-Soluble Zinc Ionophores 2

ABSTRACT: We have demonstrated that water-soluble zinc ionophores can be administered to mice at relatively high doses and inhibit the growth of A549 lung cancer cells grown in xenograft models. Gene expression profiles of tumor specimens harvested from mice four hours after treatment confirmed that the activation of stress responsive genes occurs in vivo. These findings lead us to propose that the pharmacologic delivery of zinc to tumors using water solubilized ionophores is a potential approach to cancer therapy. Keywords: Dose response

ORGANISM(S): Homo sapiens

PROVIDER: GSE6962 | GEO | 2007/02/07

SECONDARY ACCESSION(S): PRJNA104131

REPOSITORIES: GEO

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Synthesis and Anticancer Properties of Water-Soluble Zinc Ionophores 1

2007-02-07 | GSE6960 | GEO

Transcription profiling of A549 lung cancer cultures treated with the lead compound PCI-5002 supplemeted with zinc reveals synthesis and anticancer properties of water-soluble zinc ionophores

Project description:We have shown that water solubilized versions of a zinc ionophore increase intracellular concentrations of free zinc and have antiproliferative activity in exponential phase A549 lung cancer cultures. The gene expression profiles of A549 lung cancer cultures treated with the lead compound PCI-5002 reveal the activation of stress response pathways. Medium supplementation with zinc (25 Î¼M) led to activation of additional oxidative stress response as well as apoptotic pathways. We propose that the pharmacologic delivery of zinc to tumors using water solubilized ionophores is a potential approach to cancer therapy. Experiment Overall Design: A549 human lung cancer cells (1 x 105 cells per T-25 flask in 7 mL complete RPMI 1640 medium) were seeded 8 days prior to treatment of non-cycling plateau phase cultures with drug. At 4 hours prior to RNA isolation, sapphyrin PCI-5002 (10 Î¼M final concentration), ZnOAc2 (25 Î¼M final concentration), the combination, or control (5% mannitol) solution was added to the cultures. Each experiment was performed in triplicate. After incubation, all cultures were washed twice with HBSS supplemented with 0.5% BSA and total RNA was isolated and subjected to analysis on Human Genome U133 Plus 2.0 Arrays (Affymetrix, Santa Clara, CA), as described. ArrayAssist software (Stratagene/Affymetrix) and the RMA (Robust Microarray Analysis) algorithm were used to generate scaled gene expression values.

2008-06-15 | E-GEOD-6960 | biostudies-arrayexpress

Transcription profiling of human samples - synthesis and anticancer properties of water-soluble Zinc ionophore: cell culture and xenograft model (GEO Super Series)

Project description:This SuperSeries is composed of the following subset Series:; GSE6960: Synthesis and Anticancer Properties of Water-Soluble Zinc Ionophores 1; GSE6962: Synthesis and Anticancer Properties of Water-Soluble Zinc Ionophores 2 Experiment Overall Design: Refer to individual Series

2008-06-15 | E-GEOD-6972 | biostudies-arrayexpress

Synthesis and Anticancer Properties of Water-Soluble Zinc Ionophore: Cell Culture and Xenograft Model

Project description:This SuperSeries is composed of the SubSeries listed below.

2007-02-07 | GSE6972 | GEO

Synthesis and anticancer properties of water-soluble zinc ionophores.

Project description:Several water-solubilized versions of the zinc ionophore 1-hydroxypyridine-2-thione (ZnHPT), synthesized as part of the present study, have been found both to increase the intracellular concentrations of free zinc and to produce an antiproliferative activity in exponential phase A549 human lung cancer cultures. Gene expression profiles of A549 cultures treated with one of these water-soluble zinc ionophores, PCI-5002, reveal the activation of stress response pathways under the control of metal-responsive transcription factor 1 (MTF-1), hypoxia-inducible transcription factor 1 (HIF-1), and heat shock transcription factors. Additional oxidative stress response and apoptotic pathways were activated in cultures grown in zinc-supplemented media. We also show that these water-soluble zinc ionophores can be given to mice at 100 micromol/kg (300 micromol/m(2)) with no observable toxicity and inhibit the growth of A549 lung and PC3 prostate cancer cells grown in xenograft models. Gene expression profiles of tumor specimens harvested from mice 4 h after treatment confirmed the in vivo activation of MTF-1-responsive genes. Overall, we propose that water-solubilized zinc ionophores represent a potential new class of anticancer agents.

| S-EPMC3033660 | biostudies-literature

Transcription profiling of A549 lung cancer cultures treated with the lead compound PCI-5002 supplemeted with zinc reveals synthesis and anticancer properties of water-soluble zinc ionophores

Project description:We have shown that water solubilized versions of a zinc ionophore increase intracellular concentrations of free zinc and have antiproliferative activity in exponential phase A549 lung cancer cultures. The gene expression profiles of A549 lung cancer cultures treated with the lead compound PCI-5002 reveal the activation of stress response pathways. Medium supplementation with zinc (25 μM) led to activation of additional oxidative stress response as well as apoptotic pathways. We propose that the pharmacologic delivery of zinc to tumors using water solubilized ionophores is a potential approach to cancer therapy. Experiment Overall Design: A549 human lung cancer cells (1 x 105 cells per T-25 flask in 7 mL complete RPMI 1640 medium) were seeded 8 days prior to treatment of non-cycling plateau phase cultures with drug. At 4 hours prior to RNA isolation, sapphyrin PCI-5002 (10 μM final concentration), ZnOAc2 (25 μM final concentration), the combination, or control (5% mannitol) solution was added to the cultures. Each experiment was performed in triplicate. After incubation, all cultures were washed twice with HBSS supplemented with 0.5% BSA and total RNA was isolated and subjected to analysis on Human Genome U133 Plus 2.0 Arrays (Affymetrix, Santa Clara, CA), as described. ArrayAssist software (Stratagene/Affymetrix) and the RMA (Robust Microarray Analysis) algorithm were used to generate scaled gene expression values.

| S-ECPF-GEOD-6960 | biostudies-other

Design and Anticancer Properties of New Water-Soluble Ruthenium-Cyclopentadienyl Complexes.

Project description:Ruthenium complexes are emerging as one of the most promising classes of complexes for cancer therapy. However, their limited aqueous solubility may be the major limitation to their potential clinical application. In view and to contribute to the progress of this field, eight new water-soluble Ru(II) organometallic complexes of general formula [RuCp(mTPPMS)n(L)] [CF3SO3], where mTPPMS = diphenylphosphane-benzene-3-sulfonate, for n = 2, L is an imidazole-based ligand (imidazole, 1-benzylimidazole, 1-butylimidazole, (1-(3-aminopropyl)imidazole), and (1-(4-methoxyphenyl)imidazole)), and for n = 1, L is a bidentate heteroaromatic ligand (2-benzoylpyridine, (di(2-pyridyl)ketone), and (1,2-(2-pyridyl)benzo-[b]thiophene)) were synthesized and characterized. The new complexes were fully characterized by NMR, FT-IR, UV-vis., ESI-HRMS, and cyclic voltammetry, which confirmed all the proposed molecular structures. The antiproliferative potential of the new Ru(II) complexes was evaluated on MDAMB231 breast adenocarcinoma, A2780 ovarian carcinoma, and HT29 colorectal adenocarcinoma cell lines, showing micromolar (MDAMB231 and HT29) and submicromolar (A2780) IC50 values. The interaction of complex 6 with human serum albumin (HSA) and fatty-acid-free human serum albumin (HSAfaf) was evaluated by fluorescence spectroscopy techniques, and the results revealed that the ruthenium complex strongly quenches the intrinsic fluorescence of albumin in both cases.

| S-EPMC9321894 | biostudies-literature

Synthesis and optical properties of water-soluble biperylene-based dendrimers.

Project description:We report the synthesis and photophysical properties of three biperylene-based dendrimers, which show red fluorescence in water. A fluorescence microscopy study demonstrated uptake of biperylene-based dendrimers in living cells. Our results indicate that these biperylene-based dendrimers are promising candidates in fluorescence imaging applications with the potential as therapeutic carriers.

| S-EPMC4037920 | biostudies-literature

Water-Soluble Polymer

Project description:Water-Soluble Polymer Raw sequence reads

| PRJNA1039989 | ENA

Dynamic transcriptomic profiles of zebrafish gills in response to zinc depletion

Project description:Zinc deficiency is detrimental to organisms highlighting its role as an essential micronutrient contributing to numerous biological processes. To investigate the underlying molecular events invoked by zinc depletion we performed a temporal analysis of transcriptome changes observed within zebrafish gill. This tissue represents a model system for studying ion absorption across polarised cells as it provides a major pathway for fish to acquire zinc directly from water whilst sharing a conserved zinc transporting system with mammals. Zebrafish were treated with either zinc-depleted (water = 2.61 μg L-1; diet = 26 mg kg-1) or zinc-adequate (water = 16.3 μg L-1; diet = 233 mg kg-1) conditions for two weeks. Gill samples were collected at five time points and transcriptome changes analysed in quintuplicate using a 16K oligonucleotide array.

2010-05-20 | GSE21894 | GEO

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