Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.6.3.44 (
P-glycoprotein
)
13,344
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Dolastatin 10
, a cytotoxic pentapeptide isolated from the mollusk Dolabella auricularia, exhibits potent antitumor activity. The present studies demonstrated that sublines of murine PC4 and human U-937 leukemia cells expressing a multidrug resistance (MDR) phenotype are cross-resistant to this agent. We also demonstrated that such resistance was reversed by verapamil. While these findings suggested the involvement of the
P-glycoprotein
(
P-gp
) in dolastatin 10 resistance, we performed similar studies in a CHO cell line transfected with the human mdr1 cDNA. Expression of
P-gp
in the transfected cells was associated with resistance to dolastatin 10 by a verapamil-sensitive mechanism. The demonstration that photoaffinity labeling of
P-gp
was decreased in the presence of dolastatin 10 further supports the interaction of this cytotoxic peptide with
P-gp
. Taken together, these findings suggest that resistance to dolastatin 10 is conferred, at least in part, by
P-gp
and that this cytotoxic peptide is a novel member of the MDR phenotype.
...
PMID:Role of P-glycoprotein in dolastatin 10 resistance. 791 13
