Thyroid hormones induce expression of enzymes involved in chemotherapy drug metabolism

DIAZ FLAQUE MC ; CAYROL F; ASCHERO R; STERLE H; VALLI E; BELARDI F; PAULAZO A; KLECHA A; BARREIRO ARCOS ML; ELIZALDE PV; CREMASCHI GA

Chicago

Congreso; 16th International Congress of Endocrinology, ICE/ENDO 2014; 2014

Endocrine Society

The cytochrome P450 (CYP) enzymes belong to a family of proteins that metabolize drugs used in chemotherapy. It is crucial to know the pattern of expression of these enzymes in each patient when starting the chemotherapy for 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 tissues. We recently showed that THs stimulate the proliferation and activity of T cells. We also found that THs modulate these functions by activating both canonical nuclear (TR) and membrane receptors (mTR, represented by integrin alphavβ3). 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 and cell impermeable agarose-bound T3/T4 (TH-ag). CYP expression was assessed in the LCT human cell line, Jurkat. Treatment for 18 hours with THs- free and TH-ag induced a 4-fold increase of CYP 3A4 mRNA (n = 5, p