Modulators and substrates of P-glycoprotein and cytochrome P4503A coordinately up-regulate these proteins in human colon carcinoma cells.

Article Details

Citation

Schuetz EG, Beck WT, Schuetz JD

Modulators and substrates of P-glycoprotein and cytochrome P4503A coordinately up-regulate these proteins in human colon carcinoma cells.

Mol Pharmacol. 1996 Feb;49(2):311-8.

PubMed ID
8632764 [ View in PubMed
]
Abstract

Xenobiotics frequently induce proteins involved in their detoxification. Because many drugs that are metabolized by human cytochromes P450 (CYP) 3A4 and 3A5 are also transported by the drug efflux pump P-glycoprotein, we determined whether expression of these proteins was altered by a variety of drugs in a cell line derived from a human colon adenocarcinoma, LS180/WT, and its adriamycin-resistant subline, LS180/AD50. P-glycoprotein and CYP3A4 were constitutively expressed in both LS180/AD50 and LS180/WT cells, and both proteins were up-regulated after treatment with many drugs, including rifampicin, phenobarbital, clotrimazole, reserpine, and isosafrole. However, there were some exceptions because P-glycoprotein was up-regulated by midazolam and nifedipine, whereas CYP3A4 was not. CYP3A5, which is also constitutively expressed in these cells, remained unchanged with most drug treatments but was up-regulated by reserpine and clotrimazole. The apparent coordinated coexpression of the CYP3A gene family and P-glycoprotein in the LS180 cells suggests that for common orally administered drugs, P-glycoprotein may play an important role in net drug absorption and drug/drug interactions of shared CYP3A4/P-glycoprotein substrates.

DrugBank Data that Cites this Article

Drug Enzymes
DrugEnzymeKindOrganismPharmacological ActionActions
ReserpineCytochrome P450 3A5ProteinHumans
Unknown
Inducer
Details
Drug Transporters
DrugTransporterKindOrganismPharmacological ActionActions
AmiodaroneP-glycoprotein 1ProteinHumans
Unknown
Inhibitor
Inducer
Details
ClotrimazoleP-glycoprotein 1ProteinHumans
Unknown
Inhibitor
Inducer
Details
PhenobarbitalP-glycoprotein 1ProteinHumans
Unknown
Substrate
Inducer
Details
ReserpineP-glycoprotein 1ProteinHumans
Unknown
Substrate
Inhibitor
Inducer
Details
RifampicinP-glycoprotein 1ProteinHumans
Unknown
Inducer
Details
SirolimusP-glycoprotein 1ProteinHumans
Unknown
Inhibitor
Inducer
Details
TacrolimusP-glycoprotein 1ProteinHumans
Unknown
Substrate
Inhibitor
Inducer
Details
Pharmaco-proteomics
DrugDrug GroupsGeneGene IDChangeInteractionChromosome
RifampicinApprovedCYP3A41576
increased
Rifampin results in increased expression of CYP3A4 protein7q22.1
RifampicinApprovedCYP3A41576
increased
Rifampin results in increased expression of CYP3A4 protein7q22.1
RifampicinApprovedCYP3A41576
increased
Rifampin results in increased expression of CYP3A4 protein7q22.1
PhenobarbitalApproved InvestigationalCYP3A41576
increased
Phenobarbital results in increased expression of CYP3A4 protein7q22.1
RifampicinApprovedABCB15243
increased
Rifampin results in increased expression of ABCB1 protein7q21.12