Thyroid Hormones Induce Expression of Enzymes Involved in Chemotherapy Drug Metabolism

DIAZ FLAQUÉ C.; CAYROL M.F.; ASCHERO R; STERLE H.A.; VALLI E.; BELARDI F; PAULAZO M.A.; KLECHA A.J.; BARREIRO ARCOS M.L.; ELIZALDE P; CREMASCHI G.A.

Chicago

Congreso; 16th International Congress of Endocrinology & the Endocrine Societys 96th Annual Meeting & Expo; 2014

The cytochrome P450 (CYP) enzymes belong to a family of proteins that metabolize drugs used in chemotherapy, and is crucial to know the pattern of expression of these enzymes in each patient when starting chemotherapy to predict its effectiveness. Thyroid hormones (TH)?3,5,30-triiodo-L-thyronine (T3) and L-thyroxine (T4)? are important regulators of the metabolism and physiology of most normal tissues. We recently showed that THs stimulate the proliferation and metabolism of T cells. We also found that THs modulate these functions by activating both canonical nuclear (TR) and membrane receptors (mTR, represented by integrin avβ3). In the present work, we studied the ability of THs to induce the expression of the CYP enzymes in human T-cell lymphomas (TCL). To differentiate between nuclear vs. membrane-initiated effects, TCL cells were treated with physiological concentrations of free (TH-free) or cell impermeable agarose-bound T3/T4 (TH-ag). CYP expression was assessed in the TCL human cell line Jurkat by measuring CYP3A4 mRNA levels. Treatment for 18 hours with TH- free and TH-ag induced a 4-fold increase in CYP 3A4 mRNA (n = 5, p