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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
19
pubmed:dateCreated
2010-9-20
pubmed:abstractText
The process of cancer development consists of three sequential stages termed initiation, promotion, and progression. Oxidative stress damages DNA and introduces mutations into oncogenes or tumor suppressor genes, thus contributing to cancer development. Cancer chemoprevention is defined to prevent or delay the development of cancer by the use of natural or synthetic substances. In the present study, we synthesized a series of organoselenium compounds and evaluated their possible chemopreventive properties in human prostate cancer LNCaP cells. Among 42 organoselenium compounds tested, two compounds, 3-selena-1-dethiacephem 13 and 3-selena-1-dethiacephem 14 strongly activated the Nrf2/ARE (antioxidant response element) signaling and thus markedly increased expression of heme oxygenase-1 (HO-1), a phase II antioxidant enzyme. Translocation of Nrf2 to the nucleus preceded HO-1 protein induction by two compounds. The intracellular ROS level was strongly reduced immediately after treatment with these compounds, showing that they are potent antioxidants. Finally, both compounds inhibited cell growth via cell cycle arrest. Our findings suggest that compounds 13 and 14 could not only attenuate oxidative stress through Nrf2/ARE activation and direct ROS scavenging but also inhibit cell growth. Thus, these compounds possess the potential as pharmacological agents for chemoprevention of human prostate cancer.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1464-3391
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7001-8
pubmed:meshHeading
pubmed-meshheading:20805033-Antineoplastic Agents, pubmed-meshheading:20805033-Cell Cycle, pubmed-meshheading:20805033-Cell Line, Tumor, pubmed-meshheading:20805033-Cell Proliferation, pubmed-meshheading:20805033-Drug Screening Assays, Antitumor, pubmed-meshheading:20805033-Heme Oxygenase-1, pubmed-meshheading:20805033-Humans, pubmed-meshheading:20805033-Male, pubmed-meshheading:20805033-Molecular Conformation, pubmed-meshheading:20805033-NF-E2-Related Factor 2, pubmed-meshheading:20805033-Organoselenium Compounds, pubmed-meshheading:20805033-Oxidative Stress, pubmed-meshheading:20805033-Prostatic Neoplasms, pubmed-meshheading:20805033-Reactive Oxygen Species, pubmed-meshheading:20805033-Signal Transduction, pubmed-meshheading:20805033-Stereoisomerism, pubmed-meshheading:20805033-Structure-Activity Relationship
pubmed:year
2010
pubmed:articleTitle
Identification of organoselenium compounds that possess chemopreventive properties in human prostate cancer LNCaP cells.
pubmed:affiliation
Department of Longevity and Aging Research, Gifu International Institute of Biotechnology, 1-1 Naka-fudogaoka, Kakamigahara, Gifu 504-0838, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't