Dataset Information


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

ABSTRACT: 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.

INSTRUMENT(S): 418 [Affymetrix]

ORGANISM(S): Homo sapiens  

SUBMITTER: Joseph Gerard Hacia  

PROVIDER: E-GEOD-6960 | ArrayExpress | 2008-06-15



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