|
rdf:type |
|
|
lifeskim:mentions |
umls-concept:C0008838,
umls-concept:C0011065,
umls-concept:C0038952,
umls-concept:C0086418,
umls-concept:C0332324,
umls-concept:C0332325,
umls-concept:C0334227,
umls-concept:C1140680,
umls-concept:C1704259,
umls-concept:C1705987,
umls-concept:C2349975
|
|
pubmed:issue |
10
|
|
pubmed:dateCreated |
2006-9-7
|
|
pubmed:abstractText |
RRR-alpha-tocopherol ether linked acetic acid analog (alpha-TEA), is a potential chemotherapeutic agent for ovarian cancer. Pro-death and pro-life signaling pathways were studied to understand the anti-cancer actions of alpha-TEA on cisplatin-sensitive (A2780S) and -resistant (A2780/cp70R) human ovarian cancer cells. Both cell lines were refractory to Fas; whereas, alpha-TEA sensitized them to Fas signaling. alpha-TEA increased levels of Fas message, protein and membrane-associated Fas. Neutralizing antibodies to Fas or Fas L partially blocked alpha-TEA-induced apoptosis. alpha-TEA induced prolonged activation of c-Jun N-terminal kinase (JNK) and its substrate c-Jun; Bax conformational change; and cleavage of Bid and caspases-8, -9 and -3. Chemical inhibitors of JNK, and caspases blocked alpha-TEA-induced apoptosis. alpha-TEA decreased phosphorylation of protein kinase B (Akt/PKB) and extracellular signal-regulated kinase (ERK1/2), as well as cellular FLICE-like inhibitory protein (c-FLIP) and Survivin protein levels. Knockdown of Akt and ERK activity using phosphoinositide- 3-kinase (PI3K) and mitogen-activated protein kinase kinase (MKK1) inhibitors enhanced alpha-TEA-induced apoptosis. Over-expression of constitutively active Akt2 and MKK1 blocked alpha-TEA-induced apoptosis. Collectively, data show alpha-TEA to be a potent apoptotic inducer of both cisplatin-sensitive and -resistant human ovarian cancer cells via activating death receptor Fas signaling and suppressing anti-apoptotic AKT and ERK targets.
|
|
pubmed:grant |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2,5,7,8-tetramethyl-2R-(4R,8R,12-tri...,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD95,
http://linkedlifedata.com/resource/pubmed/chemical/BIRC5 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CASP8 and FADD-Like Apoptosis...,
http://linkedlifedata.com/resource/pubmed/chemical/CASP8 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 8,
http://linkedlifedata.com/resource/pubmed/chemical/Cisplatin,
http://linkedlifedata.com/resource/pubmed/chemical/Extracellular Signal-Regulated MAP...,
http://linkedlifedata.com/resource/pubmed/chemical/FAS protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Inhibitor of Apoptosis Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/JNK Mitogen-Activated Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/Microtubule-Associated Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Oncogene Protein v-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-jun,
http://linkedlifedata.com/resource/pubmed/chemical/Tocopherols,
http://linkedlifedata.com/resource/pubmed/chemical/Vitamin E
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Oct
|
|
pubmed:issn |
1360-8185
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:volume |
11
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
1813-23
|
|
pubmed:dateRevised |
2011-11-17
|
|
pubmed:meshHeading |
pubmed-meshheading:16850165-Adenocarcinoma,
pubmed-meshheading:16850165-Antigens, CD95,
pubmed-meshheading:16850165-Apoptosis,
pubmed-meshheading:16850165-CASP8 and FADD-Like Apoptosis Regulating Protein,
pubmed-meshheading:16850165-Caspase 8,
pubmed-meshheading:16850165-Cell Survival,
pubmed-meshheading:16850165-Cisplatin,
pubmed-meshheading:16850165-Down-Regulation,
pubmed-meshheading:16850165-Drug Resistance, Neoplasm,
pubmed-meshheading:16850165-Enzyme Activation,
pubmed-meshheading:16850165-Extracellular Signal-Regulated MAP Kinases,
pubmed-meshheading:16850165-Female,
pubmed-meshheading:16850165-Humans,
pubmed-meshheading:16850165-Inhibitor of Apoptosis Proteins,
pubmed-meshheading:16850165-JNK Mitogen-Activated Protein Kinases,
pubmed-meshheading:16850165-Microtubule-Associated Proteins,
pubmed-meshheading:16850165-Mitochondria,
pubmed-meshheading:16850165-Neoplasm Proteins,
pubmed-meshheading:16850165-Oncogene Protein v-akt,
pubmed-meshheading:16850165-Ovarian Neoplasms,
pubmed-meshheading:16850165-Proto-Oncogene Proteins c-jun,
pubmed-meshheading:16850165-Signal Transduction,
pubmed-meshheading:16850165-Tocopherols,
pubmed-meshheading:16850165-Tumor Cells, Cultured,
pubmed-meshheading:16850165-Vitamin E
|
|
pubmed:year |
2006
|
|
pubmed:articleTitle |
alpha-TEA inhibits survival and enhances death pathways in cisplatin sensitive and resistant human ovarian cancer cells.
|
|
pubmed:affiliation |
School of Biological Sciences/C0900, University of Texas at Austin, 78712, USA.
|
|
pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, N.I.H., Extramural
|
