TY - JOUR
T1 - Effects of PPARγ agonists on cell survival and focal adhesions in a Chinese thyroid carcinoma cell line
AU - Chen, Ying
AU - Wang, Seu Mei
AU - Wu, Jiahn Chun
AU - Huang, Shih Horng
PY - 2006/7/1
Y1 - 2006/7/1
N2 - Peroxisome proliferator-activated receptor γ(PPARγ) agonists cause cell death in several types of cancer cells. The aim of this study was to examine the effects of two PPARγ agonists, ciglitazone and 15-deoxy-Δ12,14-prostaglandin J2 (15dPGJ2), on the survival of thyroid carcinoma CGTH W-2 cells. Both ciglitazone and 15dPGJ2 decreased cell viability in a time- and dose-dependent manner. Cell death was mainly due to apoptosis, with a minor contribution from necrosis. Increased levels of active caspase 3, cleaved poly (ADP-ribose) polymerase (PARP), and cytosolic cytochrome-c were noted. In addition, ciglitazone and 15dPGJ2 induced detachment of CGTH W-2 cells from the culture substratum. Both the protein levels and immunostaining signals of focal adhesion (FA) proteins, including vinculin, integrin β1, focal adhesion kinase (FAK), and paxillin were decreased after PPARγ agonist treatment. Meanwhile, reduced phosphorylation of FAK and paxillin was noted. Furthermore, PPARγ agonists induced expression of protein tyrosine phosphatase-PEST (PTP-PEST), and of phosphatase and tensin homologue deleted on chromosome ten (PTEN). The upregulation of these phosphatases might contribute to the dephosphorylation of FAK and paxillin, since pretreatment with orthovanadate prevented PPARγ agonist-induced dephosphorylation of FAK and paxillin. Perturbation of CGTH W-2 cells with anti-integrin β1 antibodies induced FA disruption and apoptosis in the same cells, thus the downregulation of integrin β1 by PPARγ agonists resulted in FA disassembly and might induce apoptosis via anoikis. Our results suggested the presence of crosstalk between apoptosis and integrin-FA signaling. Moreover, upregulation and activation of PTEN was correlated with reduced phosphorylation of Akt, and this consequence disfavored cell survival. In conclusion, PPARγ agonists induced apoptosis of thyroid carcinoma cells via the cytochrome-c caspase 3 and PTEN-Akt pathways, and induced necrosis via the PARP pathway.
AB - Peroxisome proliferator-activated receptor γ(PPARγ) agonists cause cell death in several types of cancer cells. The aim of this study was to examine the effects of two PPARγ agonists, ciglitazone and 15-deoxy-Δ12,14-prostaglandin J2 (15dPGJ2), on the survival of thyroid carcinoma CGTH W-2 cells. Both ciglitazone and 15dPGJ2 decreased cell viability in a time- and dose-dependent manner. Cell death was mainly due to apoptosis, with a minor contribution from necrosis. Increased levels of active caspase 3, cleaved poly (ADP-ribose) polymerase (PARP), and cytosolic cytochrome-c were noted. In addition, ciglitazone and 15dPGJ2 induced detachment of CGTH W-2 cells from the culture substratum. Both the protein levels and immunostaining signals of focal adhesion (FA) proteins, including vinculin, integrin β1, focal adhesion kinase (FAK), and paxillin were decreased after PPARγ agonist treatment. Meanwhile, reduced phosphorylation of FAK and paxillin was noted. Furthermore, PPARγ agonists induced expression of protein tyrosine phosphatase-PEST (PTP-PEST), and of phosphatase and tensin homologue deleted on chromosome ten (PTEN). The upregulation of these phosphatases might contribute to the dephosphorylation of FAK and paxillin, since pretreatment with orthovanadate prevented PPARγ agonist-induced dephosphorylation of FAK and paxillin. Perturbation of CGTH W-2 cells with anti-integrin β1 antibodies induced FA disruption and apoptosis in the same cells, thus the downregulation of integrin β1 by PPARγ agonists resulted in FA disassembly and might induce apoptosis via anoikis. Our results suggested the presence of crosstalk between apoptosis and integrin-FA signaling. Moreover, upregulation and activation of PTEN was correlated with reduced phosphorylation of Akt, and this consequence disfavored cell survival. In conclusion, PPARγ agonists induced apoptosis of thyroid carcinoma cells via the cytochrome-c caspase 3 and PTEN-Akt pathways, and induced necrosis via the PARP pathway.
KW - Apoptosis
KW - Focal adhesion
KW - Necrosis
KW - PPARγ agonists
UR - http://www.scopus.com/inward/record.url?scp=33745608468&partnerID=8YFLogxK
U2 - 10.1002/jcb.20839
DO - 10.1002/jcb.20839
M3 - Article
C2 - 16795079
AN - SCOPUS:33745608468
SN - 0730-2312
VL - 98
SP - 1021
EP - 1035
JO - Journal of Cellular Biochemistry
JF - Journal of Cellular Biochemistry
IS - 4
ER -
