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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2007-7-30
pubmed:abstractText
New therapeutic agents are needed for the treatment of androgen-independent prostate cancer (PrCa). We have investigated the effect of methylseleninic acid (MSA) on tumor stage-specific prostate cells derived from the C3 (1)/Tag model for PrCa: Pr111, a slow-growing and nontumorigenic cell line isolated from a prostate intraepithelial neoplasia lesion; Pr14, a tumorigenic line derived from a primary tumor; and Pr14C1, a sub-clone of Pr14 explanted from a lung metastasis. We demonstrate that MSA strongly inhibits cell growth and induces apoptosis in C3 (1)/Tag tumor cells, in a dose-dependent manner. A decrease in phosphorylated ERK1/2 and AKT was also found in tumor cells, but not in Pr111. Microarray analysis using affymetrix showed that the number of genes with an altered expression in tumor cells is significantly higher (p < 0.01) than in nontumoral cells. Pathways analyses revealed a decrease in the expression of genes involved in metabolism (Fabp5, Cyba), signal transduction (ERK, AKT), angiogenesis (neuropilin-1, Flt-4) and transcription (cAMP response element-binding protein) in tumor cells. The expression of neuropilin-1, a protein involved in VEGF signaling and tumor angiogenesis, was 97-fold repressed in Pr14 cells treated with MSA. Combination treatments using low doses of etoposide or taxotere (docetaxel), plus low doses of MSA revealed a strong enhancement of cell growth inhibition and apoptosis in tumor cells. Our in vivo studies using Pr14 cells xenografted into nude mice demonstrated that MSA significantly enhances the chemotherapeutical effect of etoposide, resulting in 78.3% tumor growth inhibition. These results suggest that MSA could be used against PrCa to enhance the effect of etoposide.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0020-7136
pubmed:author
pubmed:copyrightInfo
(c) 2007 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
121
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1197-204
pubmed:meshHeading
pubmed-meshheading:17520673-Animals, pubmed-meshheading:17520673-Antineoplastic Agents, pubmed-meshheading:17520673-Antineoplastic Combined Chemotherapy Protocols, pubmed-meshheading:17520673-Apoptosis, pubmed-meshheading:17520673-Blotting, Western, pubmed-meshheading:17520673-Cell Line, Tumor, pubmed-meshheading:17520673-Cell Proliferation, pubmed-meshheading:17520673-Dose-Response Relationship, Drug, pubmed-meshheading:17520673-Drug Synergism, pubmed-meshheading:17520673-Etoposide, pubmed-meshheading:17520673-Gene Expression, pubmed-meshheading:17520673-Gene Expression Profiling, pubmed-meshheading:17520673-Humans, pubmed-meshheading:17520673-Male, pubmed-meshheading:17520673-Metabolic Networks and Pathways, pubmed-meshheading:17520673-Mice, pubmed-meshheading:17520673-Mice, Nude, pubmed-meshheading:17520673-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:17520673-Organoselenium Compounds, pubmed-meshheading:17520673-Prostatic Neoplasms, pubmed-meshheading:17520673-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:17520673-Signal Transduction, pubmed-meshheading:17520673-Taxoids, pubmed-meshheading:17520673-Xenograft Model Antitumor Assays
pubmed:year
2007
pubmed:articleTitle
Methylseleninic acid enhances the effect of etoposide to inhibit prostate cancer growth in vivo.
pubmed:affiliation
Division of Oncology, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't