Antiproliferative and apoptotic effects of telmisartan in human colon cancer cells

摘要

Telmisartan is an angiotensin I (AT(1)) receptor blocker used in the treatment of essential hypertension, with partial peroxisome proliferator-activated receptor gamma (PPAR gamma) agonism. In prior studies, PPAR gamma activation led to apoptosis and cell cycle inhibition in various cancer cells. The aim of the present study was to investigate the potential antiproliferative and apoptotic effects of telmisartan by partially activating PPAR gamma. HT-29, SW-480 and SW-620 cells were incubated with telmisartan (0.2-5 mu M) or the full agonist, pioglitazone (0.2-5.0 mu M). The antiproliferative and apoptotic effects of telmisartan in the human colon cancer cells were significant at therapeutic serum concentrations, and telmisartan exhibited a potency at least equivalent to the full PPAR gamma agonist, pioglitazone. The antiproliferative and apoptotic effects of pioglitazone in the human colon cancer cells were not completely deregulated by PPAR gamma blockade with GW9662. In the telmisartan-treated cells, PPAR gamma blockade resulted in an increased antiproliferative and apoptotic effect. These effects are not entirely explained by PPAR gamma activation, however, possible hypotheses that require further experimental investigation are as follows: i) Ligand-independent PPAR gamma activation through the activation-function 1 domain; ii) a PPAR gamma-independent mechanism; or iii) independent antiproliferative and apoptotic effects through GW9662.