Modulators and substrates of P-glycoprotein and cytochrome P4503A coordinately up-regulate these proteins in human colon carcinoma cells.
Article Details
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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
Drug Enzyme Kind Organism Pharmacological Action Actions Reserpine Cytochrome P450 3A5 Protein Humans UnknownInducerDetails - Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Amiodarone P-glycoprotein 1 Protein Humans UnknownInhibitorInducerDetails Clotrimazole P-glycoprotein 1 Protein Humans UnknownInhibitorInducerDetails Phenobarbital P-glycoprotein 1 Protein Humans UnknownSubstrateInducerDetails Reserpine P-glycoprotein 1 Protein Humans UnknownSubstrateInhibitorInducerDetails Rifampicin P-glycoprotein 1 Protein Humans UnknownInducerDetails Sirolimus P-glycoprotein 1 Protein Humans NoSubstrateInhibitorInducerDetails Tacrolimus P-glycoprotein 1 Protein Humans UnknownSubstrateInhibitorInducerDetails - Pharmaco-proteomics
Drug Drug Groups Gene Gene ID Change Interaction Chromosome Rifampicin Approved CYP3A4 1576 increased Rifampin results in increased expression of CYP3A4 protein 7q22.1 Rifampicin Approved CYP3A4 1576 increased Rifampin results in increased expression of CYP3A4 protein 7q22.1 Rifampicin Approved CYP3A4 1576 increased Rifampin results in increased expression of CYP3A4 protein 7q22.1 Phenobarbital Approved Investigational CYP3A4 1576 increased Phenobarbital results in increased expression of CYP3A4 protein 7q22.1 Rifampicin Approved ABCB1 5243 increased Rifampin results in increased expression of ABCB1 protein 7q21.12