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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2005-8-26
pubmed:abstractText
Recent evidence suggests that inflammatory cytokines and growth factors contribute to arsenite (As)-induced human carcinogenesis. We investigated the expression of inflammatory cytokine mRNAs during the transformation process induced by chronic As exposure in non-tumorigenic human osteogenic sarcoma (N-HOS) cells using gene arrays, and results were confirmed by RT-PCR and protein arrays. Caffeic acid phenethyl ester (CAPE), a naturally occurring immunomodulating agent, was used to evaluate the role of inflammatory factors in the process of As-mediated N-HOS cell transformation and in As-transformed HOS (AsT-HOS) cells. We found that an 8-week continuous exposure of N-HOS to 0.3 microM arsenite resulted in HOS cell transformation. That exposure also caused substantial decreases in inflammatory cytokine mRNAs, such as interleukin (IL) IL-1alpha, IL-2, IL-8, IL-18, MCP-1, TGF-beta2, and TNF-alpha, while it increased c-jun mRNA in a time-dependent manner. Co-incubation of N-HOS with As and CAPE (0.5-2.5 microM) prevented As-mediated declines in cytokine mRNAs in the co-treated cells, as well as their transformation to anchorage independence, while it caused decreases in c-jun mRNA. CAPE (up to 10 microM) had no effect on growth of N-HOS cells. However, CAPE (1-10 microM) treatment of AsT-HOS cells inhibited cell growth, induced cell cycle G2/M arrest, and triggered apoptosis, accompanied by changes in cytokine gene expression, as well as decreases in cyclin B1 and cdc2 abundance. Resveratrol (RV) and (-)(.) epigallocatechin gallate (EGCG), preventive agents present in grapes and green tea, respectively, induced similar changes in AsT-HOS cell growth but required much higher doses than CAPE to cause 50% growth arrest (<2.5 microM CAPE versus 25 microM RV or 50 microM EGCG). Overall, our findings suggest that inflammatory cytokines play an important role in the suppressive effects of CAPE on As-induced cell transformation and in the selective cytotoxicity of CAPE to As-transformed HOS cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0300-483X
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
213
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
81-96
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:16085347-Antioxidants, pubmed-meshheading:16085347-Apoptosis, pubmed-meshheading:16085347-Arsenites, pubmed-meshheading:16085347-Caffeic Acids, pubmed-meshheading:16085347-Catechin, pubmed-meshheading:16085347-Cell Growth Processes, pubmed-meshheading:16085347-Cell Line, pubmed-meshheading:16085347-Cell Survival, pubmed-meshheading:16085347-Cell Transformation, Neoplastic, pubmed-meshheading:16085347-Cytokines, pubmed-meshheading:16085347-Drug Interactions, pubmed-meshheading:16085347-Flow Cytometry, pubmed-meshheading:16085347-Humans, pubmed-meshheading:16085347-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:16085347-Osteosarcoma, pubmed-meshheading:16085347-Phenylethyl Alcohol, pubmed-meshheading:16085347-RNA, Messenger, pubmed-meshheading:16085347-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:16085347-Stilbenes
pubmed:year
2005
pubmed:articleTitle
Caffeic acid phenethyl ester (CAPE) prevents transformation of human cells by arsenite (As) and suppresses growth of As-transformed cells.
pubmed:affiliation
Department of Environmental Medicine and NYU Cancer Institute, NYU School of Medicine, New York, NY 10016, USA. cfyang@spirit.gcrc.upenn.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, N.I.H., Extramural