Linked Life Data

19903849

Source:http://linkedlifedata.com/resource/pubmed/id/19903849

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
23
pubmed:dateCreated
2009-12-4
pubmed:abstractText
Combination of innocuous dietary components with anticancer drugs is an emerging new strategy for cancer chemotherapy to increase antitumor responses. Tangeretin is a citrus flavonoid known to inhibit cancer cell proliferation. Here, we show an enhanced response of A2780/CP70 and 2008/C13 cisplatin-resistant human ovarian cancer cells to various combination treatments of cisplatin and tangeretin. Pretreatment of cells with tangeretin before cisplatin treatment synergistically inhibited cancer cell proliferation. This combination was effective in activating apoptosis via caspase cascade as well as arresting cell cycle at G(2)-M phase. Moreover, phospho-Akt and its downstream substrates, e.g., NF-kappaB, phospho-GSK-3beta, and phospho-BAD, were downregulated upon tangeretin-cisplatin treatment. The tangeretin-cisplatin-induced apoptosis in A2780/CP70 cells was increased by phosphoinositide-3 kinase (PI3K) inhibition and siRNA-mediated Akt silencing, but reduced by overexpression of constitutively activated Akt and GSK-3beta inhibition. The overall results indicated that tangeretin exposure preconditions cisplatin-resistant human ovarian cancer cells for a conventional response to low-dose cisplatin-induced cell death occurring through downregulation of PI3K/Akt signaling pathway. Thus, effectiveness of tangeretin combinations, as a promising modality in the treatment of resistant cancers, warrants systematic clinical studies.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1538-7445
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
69
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8910-7
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed-meshheading:19903849-Antineoplastic Combined Chemotherapy Protocols, pubmed-meshheading:19903849-Apoptosis, pubmed-meshheading:19903849-Cell Division, pubmed-meshheading:19903849-Cell Growth Processes, pubmed-meshheading:19903849-Cisplatin, pubmed-meshheading:19903849-Down-Regulation, pubmed-meshheading:19903849-Drug Administration Schedule, pubmed-meshheading:19903849-Drug Synergism, pubmed-meshheading:19903849-Female, pubmed-meshheading:19903849-Flavones, pubmed-meshheading:19903849-G2 Phase, pubmed-meshheading:19903849-Glycogen Synthase Kinase 3, pubmed-meshheading:19903849-Humans, pubmed-meshheading:19903849-Oncogene Protein v-akt, pubmed-meshheading:19903849-Ovarian Neoplasms, pubmed-meshheading:19903849-Phosphatidylinositol 3-Kinases, pubmed-meshheading:19903849-Signal Transduction
pubmed:year
2009
pubmed:articleTitle
Tangeretin sensitizes cisplatin-resistant human ovarian cancer cells through downregulation of phosphoinositide 3-kinase/Akt signaling pathway.
pubmed:affiliation
Division of Radiobiology, Department of Radiology, The Ohio State University, Columbus, Ohio 43210, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural