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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2004-4-20
pubmed:abstractText
Cancer chemotherapeutic strategies should be devised to provide higher tumor response and lower toxicity for combination chemotherapy. Genistein has been shown to inhibit the growth of various cancer cells in vitro and in vivo without toxicity to normal cells. The antitumor effects of genistein could be in part due to inactivation of NF-kappaB activity. In contrast, chemotherapeutic agents inadvertently induce NF-kappaB activity, which may lead to chemoresistance. In this study, we investigated whether the inactivation of NF-kappaB by genistein would enhance the efficacy of chemotherapeutic agents. BxPC-3 pancreatic cancer cells were pretreated with 30 micromol/L genistein for 24 hours and then exposed to lower concentrations of chemotherapeutic agents for an additional 24 hours. Cell growth inhibition assay, apoptosis assay, and NF-kappaB EMSA were performed. The combination of 30 micromol/L genistein with 1 nmol/L docetaxel or 100 nmol/L cisplatin elicited significantly greater inhibition of cell growth compared with either agent alone. The combination treatment induced more apoptosis in BxPC-3 cells compared with single agents. Moreover, the NF-kappaB activity was significantly increased within 2 hours of docetaxel or cisplatin treatment, and the NF-kappaB-inducing activity of these agents was completely abrogated in cells pretreated with genistein. These results clearly suggest that genistein pretreatment, which inactivates NF-kappaB activity, together with other cellular effects of genistein, may contribute to increased cell growth inhibition and apoptosis inducing effects of nontoxic doses of docetaxel and cisplatin, which could be a novel strategy for the treatment of pancreatic cancer.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1536-4828
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
e90-5
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Apoptosis-inducing effect of chemotherapeutic agents is potentiated by soy isoflavone genistein, a natural inhibitor of NF-kappaB in BxPC-3 pancreatic cancer cell line.
pubmed:affiliation
Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.