Pioglitazone, a synthetic ligand for PPARgamma, induces apoptosis in RB-deficient human colorectal cancer cells.
No published data are available about the expression of peroxisome proliferator-activated receptor gamma (PPARgamma) and the role of PPARgamma in retinoblastoma protein (RB)-deficient human colorectal cancer (CRC) cells (SNU-C4 and SNU-C2A). Our aim was to investigate whether PPARgamma is expressed in SNU-C4 and SNU-C2A cells and to elucidate possible molecular mechanisms underlying the effect of pioglitazone, a synthetic ligand for PPARgamma, on cell growth in these cell lines. RT-PCR and Western blot analysis showed that both human CRC cell lines expressed PPARgamma mRNA and protein. Pioglitazone inhibited the cell growth of both cell lines through G2/M phase block and apoptosis. In addition, pioglitazone caused a down-regulation of the X chromosome-linked inhibitor of apoptosis (XIAP), Bcl-2, and cyclooxygenase-2 (COX-2) under conditions leading to PPARgamma down-regulation. These results suggest that pioglitazone may have therapeutic relevance or significance in the treatment of human CRC, and the down-regulation of XIAP, Bcl-2, and COX-2 may contribute to pioglitazone-induced apoptosis in these and other RB-deficient cell lines and tumors.
Lee
C J
CJ
Department of Biochemistry, Department of Biochemistry, Dong-A University College of Medicine, Busan, South Korea.
Han
J S
JS
Seo
C Y
CY
Park
T H
TH
Kwon
H C
HC
Jeong
J S
JS
Kim
I H
IH
Yun
J
J
Bae
Y S
YS
Kwak
J Y
JY
Park
J I
JI
D017209:Apoptosis / Q000502:physiology*; D020169:Caspases / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D007004:Hypoglycemic Agents / Q000378:metabolism*; D008024:Ligands; D047495:PPAR gamma / Q000378:metabolism*; D000077205:Pioglitazone; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism*; D045162:Thiazolidinediones / Q000378:metabolism*
D018797:Cell Cycle Proteins; D007004:Hypoglycemic Agents; D008024:Ligands; D047495:PPAR gamma; D016160:Retinoblastoma Protein; D045162:Thiazolidinediones; D045304:Cytochromes c; D051546:Cyclooxygenase 2; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases; D000077205:Pioglitazone