Ciglitazone enhances ovarian cancer cell death via inhibition
of glucose transporter-1
- Author(s)
- So Jin Shin; Jin Young Kim; Sun Young Kwon; Kyo-Cheol Mun; Chi Heum Cho; Eunyoung Ha
- Keimyung Author(s)
- Shin, So Jin; Cho, Chi Heum; Kim, Jin Young; Ha, Eun Young; Mun, Kyo Cheol; Kwon, Sun Young
- Department
- Dept. of Obstetrics & Gynecology (산부인과학)
Dept. of Internal Medicine (내과학)
Dept. of Biochemistry (생화학)
Dept. of Pathology (병리학)
- Journal Title
- European Journal of Pharmacology
- Issued Date
- 2014
- Volume
- 743
- Abstract
- Ciglitazone is a peroxisome proliferator-activated receptor γ (PPARγ) agonist and improves insulin sensitivity. Apart from antidiabetic activity, ciglitazone elicits inhibitory effects on cancer cell growth. Recent studies indicate that glucose metabolism plays a key role in malignant diseases. Significant increase in glucose consumption is found under malignant conditions. The role of ciglitazone in cancer cell death in relation to glucose metabolism is unclear. Thus we designed this study to determine the effect of ciglitazone on glucose metabolism. First, we found ciglitazone inhibited glucose uptake in ovarian cancer cells but did not affect hexokinase activity. Ciglitazone decreased expression levels of glucose transporter-1 (GLUT-1). We also found that ciglitazone and siGLUT-1 treatments induced cell death in ovarian cancer cells. We identified that ciglitazone decreased expressions of specific protein 1 (Sp-1) and β-catenin while increased phosphorylation levels of AMP-activated protein kinase. In vivo study using NOD-scid IL2Rgammanull mice confirmed that ciglitazone significantly decreased ovarian cancer mass transplanted onto the back of the mice. Finally, we determined GLUT-1 expressions in patients with serous type ovarian cancer and found that GLUT-1 expression was markedly increased in cancer patients and expression level was proportional to the degree of cancer stages. These results suggest that ciglitazone induces apoptosis in ovarian cancer cells by the inhibition of GLUT-1 and provides a possible therapeutic effect of ciglitazone as an adjuvant drug in the treatment of ovarian cancer.
Keywords
Ciglitazone;
Glucose transporter-1;
Ovarian cancer;
Cell death
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