Abstract
Telmisartan is an angiotensin I (AT1) receptor blocker used in the treatment of essential hypertension, with partial peroxisome proliferator-activated receptor γ (PPARγ) agonism. In prior studies, PPARγ 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 PPARγ. HT-29, SW-480 and SW-620 cells were incubated with telmisartan (0.2–5 μM) or the full agonist, pioglitazone (0.2–5.0 μM). 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 PPARγ agonist, pioglitazone. The antiproliferative and apoptotic effects of pioglitazone in the human colon cancer cells were not completely deregulated by PPARγ blockade with GW9662. In the telmisartan-treated cells, PPARγ blockade resulted in an increased antiproliferative and apoptotic effect. These effects are not entirely explained by PPARγ activation, however, possible hypotheses that require further experimental investigation are as follows: i) Ligand-independent PPARγ activation through the activation-function 1 domain; ii) a PPARγ-independent mechanism; or iii) independent antiproliferative and apoptotic effects through GW9662.
Highlights
Telmisartan is an antihypertensive drug that exerts its effect by antagonizing the angiotensin I (AT1) receptor blocker (ARB)
Telmisartan is an ARB and a common antihypertensive drug with partial PPARγ‐agonism [1]. It is of note whether telmisartan partially activates PPARγ1 in colon cancer cells, subsequently inducing a reduction in cell viability, inhibiting cell proliferation and inducing apoptosis
PPARγ blockage with GW9662 in the presence of telmisartan as a partial PPARγ agonist did not lead to the diminished inhibition of the cell proliferation and cell viability of pioglitazone
Summary
Telmisartan is an antihypertensive drug that exerts its effect by antagonizing the angiotensin I (AT1) receptor blocker (ARB). Beyond this mechanism, Shupp et al [1] revealed partial peroxisome proliferator‐activated receptor (PPAR) agonism in 3T3‐L1 preadipocytes. PPARγ1 is present in human urological cancer cells (i.e., renal cell, prostate, bladder and testicular cancer) [4] and colon cancer cells [5], where ligand‐dependent activation by antidiabetic drugs, such as thiazolidinediones, which include pioglitazone, rosiglitazone, troglitazone and ciglitazone, leads to apoptosis [6] and an antiproliferative effect [7]
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