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The importance of acetyl coenzyme A synthetase for 11C-acetate uptake and cell survival in hepatocellular carcinoma

 Mijin Yun  ;  Seong-Hye Bang  ;  Jae Woo Kim  ;  Jun Young Park  ;  Kyoung Sup Kim  ;  Jong Doo Lee 
 JOURNAL OF NUCLEAR MEDICINE, Vol.50(8) : 1222-1228, 2009 
Journal Title
Issue Date
Acetate-CoA Ligase/metabolism* ; Acetates/pharmacokinetics* ; Adult ; Aged ; Carbon/pharmacokinetics* ; Carcinoma, Hepatocellular/diagnostic imaging ; Carcinoma, Hepatocellular/metabolism* ; Cell Line, Tumor ; Cell Survival ; Fatty Acid Synthases/metabolism* ; Female ; Fluorodeoxyglucose F18/pharmacokinetics* ; Humans ; Liver Neoplasms/diagnostic imaging ; Liver Neoplasms/metabolism* ; Male ; Metabolic Clearance Rate ; Middle Aged ; Radionuclide Imaging ; Radiopharmaceuticals/pharmacokinetics*
18F-FDG ; 11C-acetate ; fatty acid synthesis ; hepatocellular carcinoma ; acetyl CoA synthetase
We analyzed the pattern of (11)C-acetate and (18)F-FDG uptake on PET/CT in patients with hepatocellular carcinoma (HCC). We also assessed the expression of important regulatory enzymes related to glycolysis and lipid synthesis in relation to (18)F-FDG and (11)C-acetate uptake in human HCC cell lines. The significance of (11)C-acetate uptake regulation was further evaluated with regard to cell viability. METHODS: (18)F-FDG and (11)C-acetate uptake patterns in HCC in 11 patients and in 5 HCC cell lines were assessed. We evaluated the gene expression of metabolic enzymes related to glycolysis and lipid synthesis in a cell line with the highest (18)F-FDG uptake and another cell line with the highest (11)C-acetate uptake. They included hexokinase II, adenosine triphosphate citrate lyase, acetyl coenzyme A (CoA) synthetase 1 (ACSS1), acetyl CoA synthetase 2 (ACSS2), acetyl CoA carboxylase, and fatty acid synthase. In a cell line with high (11)C-acetate uptake, the enzymatic activities of ACSS1 and ACSS2 were blocked using respective small, interfering RNAs (siRNAs), and the impact on (11)C-acetate uptake and cell viability was assessed. RESULTS: In all 11 patients and 4 of the 5 cell lines, the uptake patterns of the 2 radiotracers were complementary. ACSS1 and ACSS2 were highly expressed in a cell line with low (18)F-FDG uptake and high (11)C-acetate uptake, whereas only ACSS2 was expressed in a cell line with high (18)F-FDG uptake and low (11)C-acetate uptake. Fatty acid synthase expression was seen in cells with high (18)F-FDG or (11)C-acetate uptake. These findings indicate the possibility that both glucose and acetate can be a compensatory carbon source for lipid synthesis in cancer. Transient transfection with ACSS1 or ACSS2 siRNA in cells with high (11)C-acetate uptake decreased (11)C-acetate uptake and cell viability. CONCLUSION: The patterns of (18)F-FDG and (11)C-acetate uptake seemed to complement each other in both human HCC and HCC cell lines. Fatty acid synthase expression was seen in cells with high (18)F-FDG or (11)C-acetate uptake, suggesting glucose- or acetate-dependent lipid synthesis. Acetyl CoA synthetase appears to be important in (11)C-acetate uptake and acetate-dependent lipid synthesis for the growth of cancer cells with a low-glycolysis phenotype. Inhibition of acetyl CoA synthetase in these cells may be promising for anticancer treatment
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1. College of Medicine (의과대학) > Dept. of Nuclear Medicine (핵의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Sup(김경섭) ORCID logo https://orcid.org/0000-0001-8483-8537
Kim, Jae Woo(김재우) ORCID logo https://orcid.org/0000-0001-5456-9495
Park, Jun Young(박준영) ORCID logo https://orcid.org/0000-0003-3403-2767
Yun, Mi Jin(윤미진) ORCID logo https://orcid.org/0000-0002-1712-163X
Lee, Jong Doo(이종두)
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