Inhibition of β-oxidative respiration is a therapeutic window associated with the cancer chemo-preventive activity of PPARγ agonists
Inhibition of β-oxidative respiration is a therapeutic window associated with the cancer chemo-preventive activity of PPARγ agonists
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DOI：
10.1016/j.febslet.2005.01.082
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发表时间：
2005-03-14
期刊：
影响因子：
3.5
通讯作者：
Rosier, RN
中科院分区：
文献类型：
--
作者：
Andela, VB;Altuwaijri, S;Rosier, RN
我们展示了PPARγ激动剂曲格列酮(Tro)[0-100µM]对小鼠肺泡癌细胞株(LINE 1)PPARγ和脂酶(HMG-CoA合成酶、HMG-CoA还原酶和脂肪酸合成酶)的表达和协同诱导作用。我们推测，tro诱导细胞能量代谢向脂肪酸氧化(β-氧化呼吸)转变。因此，与tro[30muM]和增加β-氧化抑制剂曲美他嗪(TMZ)[0.1-3 mM]的浓度共同处理，会导致剂量依赖性的细胞ATP水平下降和剂量依赖性的诱导细胞凋亡。这些发现表明，抑制β-氧化呼吸是与PPAR伽马激动剂的癌症化学预防活性相关的治疗窗口。(C)2005年欧洲生化学会联合会。爱思唯尔出版，版权所有。
We demonstrate expression and coordinate induction of PPAR gamma and lipogenic enzymes (HMG-CoA synthase, HMG-CoA reductase and fatty acid synthase) in a murine lung alveolar carcinoma cell line (Line 1) treated with the PPAR gamma agonist troglitazone (TRO) [0-100 mu M]. We postulate that TRO induces a shift in cellular energy metabolism towards fatty acid oxidation (beta-oxidative respiration). Accordingly, co-treatment with TRO [30 mu M] and increasing concentrations of trimetazidine (TMZ) [0.1-3 mM], an inhibitor of beta-oxidation, results in a dose dependent decrease cellular ATP levels and a dose dependent induction of apoptosis. These findings, suggest that inhibition of beta-oxidative respiration is a therapeutic window associated with the cancer chemo-preventive activity of PPAR gamma agonists. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.