Thyroid hormone and P-glycoprotein in tumor cells

Paul J. Davis, Sandra Incerpi, Hung Yun Lin, Heng Yuan Tang, Thangirala Sudha, Shaker A. Mousa

Research output: Contribution to journalReview article

13 Citations (Scopus)

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.

Original languageEnglish
Article number168427
JournalBioMed Research International
Volume2015
DOIs
Publication statusPublished - 2015

Fingerprint

P-Glycoprotein
Thyroid Hormones
Tumors
Cells
Acidification
Integrins
Neoplasms
Pumps
Thyronines
Sodium-Hydrogen Antiporter
Osteopontin
Cell Surface Receptors
Multiple Drug Resistance
Etoposide
Transcription
Calmodulin
Cell membranes
Thyroxine
Epidermal Growth Factor
Nanoparticles

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Davis, P. J., Incerpi, S., Lin, H. Y., Tang, H. Y., Sudha, T., & Mousa, S. A. (2015). Thyroid hormone and P-glycoprotein in tumor cells. BioMed Research International, 2015, [168427]. https://doi.org/10.1155/2015/168427

Thyroid hormone and P-glycoprotein in tumor cells. / Davis, Paul J.; Incerpi, Sandra; Lin, Hung Yun; Tang, Heng Yuan; Sudha, Thangirala; Mousa, Shaker A.

In: BioMed Research International, Vol. 2015, 168427, 2015.

Research output: Contribution to journalReview article

Davis, PJ, Incerpi, S, Lin, HY, Tang, HY, Sudha, T & Mousa, SA 2015, 'Thyroid hormone and P-glycoprotein in tumor cells', BioMed Research International, vol. 2015, 168427. https://doi.org/10.1155/2015/168427
Davis, Paul J. ; Incerpi, Sandra ; Lin, Hung Yun ; Tang, Heng Yuan ; Sudha, Thangirala ; Mousa, Shaker A. / Thyroid hormone and P-glycoprotein in tumor cells. In: BioMed Research International. 2015 ; Vol. 2015.
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