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rdf:type |
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lifeskim:mentions |
umls-concept:C0069717,
umls-concept:C0086418,
umls-concept:C0162638,
umls-concept:C0334227,
umls-concept:C0851285,
umls-concept:C1309143,
umls-concept:C1366876,
umls-concept:C1527249,
umls-concept:C1704259,
umls-concept:C1705987,
umls-concept:C1833235,
umls-concept:C1880177,
umls-concept:C1979930
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pubmed:issue |
2
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pubmed:dateCreated |
2008-6-3
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pubmed:abstractText |
Oxaliplatin, a chemotherapeutic drug, induces DNA strand breaks leading to apoptosis in colorectal cancer cells. gamma-H2AX is a phosphorylated histone H2AX that can act as a marker of DNA double-strand breaks (DSBs). It has been shown that securin proteins were over-expressed in a variety of cancer cells. However, the roles of gamma-H2AX and securin on the oxaliplatin-induced apoptosis in human colorectal cancer cells remain unclear. Treatment of oxaliplatin (1-10 microM for 6-24h) persistently induced gamma-H2AX formation and inhibited securin protein expression via a time- and concentration-dependent manner in HCT116 securin-wild type colorectal cancer cells. Compared with HCT116 securin-wild type cells, the induction of apoptosis and persistent gamma-H2AX formation by oxaliplatin was reduced in the HCT116 securin-null colorectal cancer cells. Furthermore, the blockage of caspases by specific caspase inhibitors reduced the levels of gamma-H2AX proteins and cytotoxicity but increased securin protein expression in the oxaliplatin-exposed cells. The gene knockdown of H2AX by transfection with a short interfering RNA of H2AX enhanced the oxaliplatin-induced cell death. Interestingly, the phosphorylation of p38 mitogen-activated protein kinase (MAPK) was markedly increased by oxaliplatin. Pre-treatment of a specific p38 MAPK inhibitor SB202190 reduced gamma-H2AX proteins and increased securin protein expression in the oxaliplatin-treated cells. Our findings suggest that p38 MAPK may oppositely regulate securin protein expression and gamma-H2AX formation in the oxaliplatin-induced apoptosis of human colorectal cancer cells.
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/4-(4-fluorophenyl)-2-(4-hydroxypheny...,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/H2AFX protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Histones,
http://linkedlifedata.com/resource/pubmed/chemical/Imidazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Organoplatinum Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridines,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/oxiplatin,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/pituitary tumor-transforming...
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0378-4274
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
30
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pubmed:volume |
179
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
63-70
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:18499365-Antineoplastic Agents,
pubmed-meshheading:18499365-Apoptosis,
pubmed-meshheading:18499365-Blotting, Western,
pubmed-meshheading:18499365-Caspases,
pubmed-meshheading:18499365-Colorectal Neoplasms,
pubmed-meshheading:18499365-Dose-Response Relationship, Drug,
pubmed-meshheading:18499365-Enzyme Inhibitors,
pubmed-meshheading:18499365-Gene Expression Regulation,
pubmed-meshheading:18499365-HCT116 Cells,
pubmed-meshheading:18499365-Histones,
pubmed-meshheading:18499365-Humans,
pubmed-meshheading:18499365-Imidazoles,
pubmed-meshheading:18499365-Microscopy, Confocal,
pubmed-meshheading:18499365-Neoplasm Proteins,
pubmed-meshheading:18499365-Organoplatinum Compounds,
pubmed-meshheading:18499365-Phosphorylation,
pubmed-meshheading:18499365-Pyridines,
pubmed-meshheading:18499365-RNA, Small Interfering,
pubmed-meshheading:18499365-Time Factors,
pubmed-meshheading:18499365-Transfection,
pubmed-meshheading:18499365-p38 Mitogen-Activated Protein Kinases
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pubmed:year |
2008
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pubmed:articleTitle |
Regulation of gamma-H2AX and securin contribute to apoptosis by oxaliplatin via a p38 mitogen-activated protein kinase-dependent pathway in human colorectal cancer cells.
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pubmed:affiliation |
Department of Life Science, Tzu Chi University, Hualien 970, Taiwan. chiusj@mail.tcu.edu.tw
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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