Thyroid Hormone and P-Glycoprotein in Tumor Cells
P-glycoprotein (P-gp; multidrug resistance pump 1, MDR1; ABCB1) is a plasma membrane efflux pump that when activated in cancer cells exports chemotherapeutic agents. Transcription of the P-gp gene (MDR1) and activity of the P-gp protein are known to be affected by thyroid hormone. A cell surface rec...
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Series: | BioMed Research International |
Online Access: | http://dx.doi.org/10.1155/2015/168427 |
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doaj-4cd83433092346cb9307113541d6daa62020-11-24T21:07:33ZengHindawi LimitedBioMed Research International2314-61332314-61412015-01-01201510.1155/2015/168427168427Thyroid Hormone and P-Glycoprotein in Tumor CellsPaul J. Davis0Sandra Incerpi1Hung-Yun Lin2Heng-Yuan Tang3Thangirala Sudha4Shaker A. Mousa5Department of Medicine, Albany Medical College, Albany, NY 12208, USADepartment of Sciences, University Roma Tre, 00146 Rome, ItalyPharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, 1 Discovery Drive, Rensselaer, NY 12144, USAPharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, 1 Discovery Drive, Rensselaer, NY 12144, USAPharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, 1 Discovery Drive, Rensselaer, NY 12144, USAPharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, 1 Discovery Drive, Rensselaer, NY 12144, USAP-glycoprotein (P-gp; multidrug resistance pump 1, MDR1; ABCB1) is a plasma membrane efflux pump that when activated in cancer cells exports chemotherapeutic agents. Transcription of the P-gp gene (MDR1) and activity of the P-gp protein are known to be affected by thyroid hormone. A cell surface receptor for thyroid hormone on integrin αvβ3 also binds tetraiodothyroacetic acid (tetrac), a derivative of L-thyroxine (T4) that blocks nongenomic actions of T4 and of 3,5,3′-triiodo-L-thyronine (T3) at αvβ3. Covalently bound to a nanoparticle, tetrac as nanotetrac acts at the integrin to increase intracellular residence time of chemotherapeutic agents such as doxorubicin and etoposide that are substrates of P-gp. This action chemosensitizes cancer cells. In this review, we examine possible molecular mechanisms for the inhibitory effect of nanotetrac on P-gp activity. Mechanisms for consideration include cancer cell acidification via action of tetrac/nanotetrac on the Na+/H+ exchanger (NHE1) and hormone analogue effects on calmodulin-dependent processes and on interactions of P-gp with epidermal growth factor (EGF) and osteopontin (OPN), apparently via αvβ3. Intracellular acidification and decreased H+ efflux induced by tetrac/nanotetrac via NHE1 is the most attractive explanation for the actions on P-gp and consequent increase in cancer cell retention of chemotherapeutic agent-ligands of MDR1 protein.http://dx.doi.org/10.1155/2015/168427 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Paul J. Davis Sandra Incerpi Hung-Yun Lin Heng-Yuan Tang Thangirala Sudha Shaker A. Mousa |
spellingShingle |
Paul J. Davis Sandra Incerpi Hung-Yun Lin Heng-Yuan Tang Thangirala Sudha Shaker A. Mousa Thyroid Hormone and P-Glycoprotein in Tumor Cells BioMed Research International |
author_facet |
Paul J. Davis Sandra Incerpi Hung-Yun Lin Heng-Yuan Tang Thangirala Sudha Shaker A. Mousa |
author_sort |
Paul J. Davis |
title |
Thyroid Hormone and P-Glycoprotein in Tumor Cells |
title_short |
Thyroid Hormone and P-Glycoprotein in Tumor Cells |
title_full |
Thyroid Hormone and P-Glycoprotein in Tumor Cells |
title_fullStr |
Thyroid Hormone and P-Glycoprotein in Tumor Cells |
title_full_unstemmed |
Thyroid Hormone and P-Glycoprotein in Tumor Cells |
title_sort |
thyroid hormone and p-glycoprotein in tumor cells |
publisher |
Hindawi Limited |
series |
BioMed Research International |
issn |
2314-6133 2314-6141 |
publishDate |
2015-01-01 |
description |
P-glycoprotein (P-gp; multidrug resistance pump 1, MDR1; ABCB1) is a plasma membrane efflux pump that when activated in cancer cells exports chemotherapeutic agents. Transcription of the P-gp gene (MDR1) and activity of the P-gp protein are known to be affected by thyroid hormone. A cell surface receptor for thyroid hormone on integrin αvβ3 also binds tetraiodothyroacetic acid (tetrac), a derivative of L-thyroxine (T4) that blocks nongenomic actions of T4 and of 3,5,3′-triiodo-L-thyronine (T3) at αvβ3. Covalently bound to a nanoparticle, tetrac as nanotetrac acts at the integrin to increase intracellular residence time of chemotherapeutic agents such as doxorubicin and etoposide that are substrates of P-gp. This action chemosensitizes cancer cells. In this review, we examine possible molecular mechanisms for the inhibitory effect of nanotetrac on P-gp activity. Mechanisms for consideration include cancer cell acidification via action of tetrac/nanotetrac on the Na+/H+ exchanger (NHE1) and hormone analogue effects on calmodulin-dependent processes and on interactions of P-gp with epidermal growth factor (EGF) and osteopontin (OPN), apparently via αvβ3. Intracellular acidification and decreased H+ efflux induced by tetrac/nanotetrac via NHE1 is the most attractive explanation for the actions on P-gp and consequent increase in cancer cell retention of chemotherapeutic agent-ligands of MDR1 protein. |
url |
http://dx.doi.org/10.1155/2015/168427 |
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