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Ciglitazone enhances ovarian cancer cell death via inhibition of glucose transporter-1

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Author(s)
So Jin ShinJin Young KimSun Young KwonKyo-Cheol MunChi Heum ChoEunyoung Ha
Keimyung Author(s)
Shin, So JinCho, Chi HeumKim, Jin YoungHa, Eun YoungMun, Kyo CheolKwon, 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
Keimyung Author(s)(Kor)
신소진
조치흠
김진영
문교철
하은영
권선영
Publisher
School of Medicine
Citation
So Jin Shin et al. (2014). Ciglitazone enhances ovarian cancer cell death via inhibition
of glucose transporter-1. European Journal of Pharmacology, 743, 17–23. doi: 10.1016/j.ejphar.2014.09.013
Type
Article
ISSN
0014-2999
Source
https://www.sciencedirect.com/science/article/pii/S0014299914006578?via%3Dihub
DOI
10.1016/j.ejphar.2014.09.013
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/35660
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Biochemistry (생화학)
1. School of Medicine (의과대학) > Dept. of Internal Medicine (내과학)
1. School of Medicine (의과대학) > Dept. of Obstetrics & Gynecology (산부인과학)
1. School of Medicine (의과대학) > Dept. of Pathology (병리학)
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