Back to Search Start Over

Thyroid Hormone and P-Glycoprotein in Tumor Cells.

Authors :
Davis, Paul J.
Incerpi, Sandra
Lin, Hung-Yun
Tang, Heng-Yuan
Sudha, Thangirala
Mousa, Shaker A.
Source :
BioMed Research International. 3/19/2015, Vol. 2015, p1-8. 8p.
Publication Year :
2015

Abstract

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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
23146133
Volume :
2015
Database :
Academic Search Index
Journal :
BioMed Research International
Publication Type :
Academic Journal
Accession number :
109273662
Full Text :
https://doi.org/10.1155/2015/168427