In:
Digestion, S. Karger AG, Vol. 64, No. 2 ( 2001), p. 75-80
Abstract:
〈 i 〉 Background/Aims: 〈 /i 〉 We investigated the effect of the peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist pioglitazone on growth and TRAIL-induced apoptosis in carcinoid cells. 〈 i 〉 Methods: 〈 /i 〉 Carcinoid cells were incubated without and with pioglitazone. Effects on growth were examined by cell count and cell cycle analysis. p21 〈 sup 〉 waf1/cip1 〈 /sup 〉 expression was determined by Western blotting. Cytotoxicity assay was performed by FACS analysis. 〈 i 〉 Results: 〈 /i 〉 Pioglitazone suppressed the growth and induced apoptosis of carcinoid cells. Additionally, pioglitazone significantly enhanced carcinoid cell death induced by tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL). The enhancement of TRAIL-induced apoptosis was associated with an upregulation of cyclin-dependent kinase inhibitor p21 〈 sup 〉 waf1/cip1 〈 /sup 〉 in pioglitazone-treated carcinoid cells. Importantly, overexpression of p21 〈 sup 〉 waf1/cip1 〈 /sup 〉 in carcinoid cells by adenoviral gene transfer of p21 sensitized them to TRAIL-induced apoptosis. 〈 i 〉 Conclusions 〈 /i 〉 : These results suggest that pioglitazone inhibits cell growth and sensitizes cells to TRAIL-induced apoptosis by induction of p21 〈 sup 〉 waf1/cip1 〈 /sup 〉 . Therefore, pioglitazone can be an effective therapeutic adjuvant for the treatment of carcinoid tumors.
Type of Medium:
Online Resource
ISSN:
0012-2823
,
1421-9867
Language:
English
Publisher:
S. Karger AG
Publication Date:
2001
detail.hit.zdb_id:
1482218-0
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