Linked Life Data

10630679

Source:http://linkedlifedata.com/resource/pubmed/id/10630679

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2000-3-3
pubmed:abstractText
In this paper, we provide direct evidence that glutathione S-transferase pi (GSTpi) detoxifies cisplatin (CDDP). We used human colonic cancer HCT8 cells sensitive and resistant to CDDP, the level of cisplatin-glutathione adduct (DDP-GSH) being higher in the resistant cells. There was an overexpression of GSTpi mRNA in these CDDP-resistant cells. Incubation of the cells with CDDP resulted in the formation of DDP-GSH dependent on the CDDP concentration and the incubation time. The formation of DDP-GSH was abolished when the cells were pre-treated with ethacrynic acid or ketoprofen, inhibitors of GSTpi. Purified GSTpi also catalyzed the formation of DDP-GSH in vitro, with an apparent Km of 0.23 mM for CDDP and an apparent Vmax of 4.9 nmol/min/mg protein. The increase in DDP-GSH produced by GSTpi was linear with incubation time up to 3 h and optimal of pH 7.4. A GSTpi transfectant cell line was constructed in HCT8 cells using a pcDNA3.1 (-)/Myc-His B with an expression vector containing cDNA for GSTpi. Transfection of GSTpi cDNA into HCT8 cells resulted in an increase in the expression of GSTpi by 1.4-fold in parallel with an augmentation of the formation of DDP-GSH. These results suggest that GSTpi plays a role in the formation of DDP-GSH and the acquisition of resistance to CDDP in cancer cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1071-5762
pubmed:author
pubmed:issnType
Print
pubmed:volume
31
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
549-58
pubmed:dateRevised
2005-11-17
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Overexpression of glutathione S-transferase pi enhances the adduct formation of cisplatin with glutathione in human cancer cells.
pubmed:affiliation
Department of Biochemistry and Molecular Biology in Disease, Atomic Bomb Disease Institute, Nagasaki University School of Medicine, Japan.
pubmed:publicationType
Journal Article