계명대학교 의학도서관 Repository

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

Metadata Downloads
Affiliated Author(s)
신소진조치흠김진영문교철하은영권선영
Alternative Author(s)
Shin, So JinCho, Chi HeumKim, Jin YoungHa, Eun YoungMun, Kyo CheolKwon, Sun Young
Journal Title
European Journal of Pharmacology
ISSN
0014-2999
Issued Date
2014
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
공개 및 라이선스
  • 공개 구분공개
  • 엠바고Forever
파일 목록

Items in Repository are protected by copyright, with all rights reserved, unless otherwise indicated.