Oleanolic acid suppresses aerobic glycolysis in cancer cells by switching pyruvate kinase type M isoforms.
Oleanolic acid suppresses aerobic glycolysis in cancer cells by switching pyruvate kinase type M isoforms.
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齐墩果酸通过转换丙酮酸激酶 M 型异构体抑制癌细胞中的有氧糖酵解
DOI：
10.1371/journal.pone.0091606
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Lin X
中科院分区：
文献类型：
--
作者：
Liu J;Wu N;Ma L;Liu M;Liu G;Zhang Y;Lin X
瓦尔堡效应是肿瘤细胞的标志之一，其特征是线粒体氧化磷酸化代谢转换为有氧糖酵解代谢。近年来，丙酮酸激酶M2（PKM 2）表达水平的增加被发现是癌细胞有氧糖酵解增强的罪魁祸首。然而，没有通过靶向PKM 2抑制有氧糖酵解的药物。在这项研究中，我们发现油酸（OA）诱导从PKM 2到PKM 1的转换，并始终消除癌细胞中的瓦尔堡效应。OA对有氧糖酵解的抑制是通过PKM 2/PKM 1开关介导的。此外，发现mTOR信号在OA处理的癌细胞中失活，并且OA对PKM 2/PKM 1开关的影响需要mTOR抑制。c-Myc依赖的hnRNPA 1和hnRNPA 1的表达减少是OA诱导PKM亚型之间转换的原因。总之，我们确定OA是一种抑制癌细胞有氧糖酵解的抗肿瘤化合物，PKM 2可能被开发为有氧糖酵解途径中的重要靶点，用于开发新型抗癌药物。
Warburg effect, one of the hallmarks for cancer cells, is characterized by metabolic switch from mitochondrial oxidative phosphorylation to aerobic glycolysis. In recent years, increased expression level of pyruvate kinase M2 (PKM2) has been found to be the culprit of enhanced aerobic glycolysis in cancer cells. However, there is no agent inhibiting aerobic glycolysis by targeting PKM2. In this study, we found that Oleanolic acid (OA) induced a switch from PKM2 to PKM1, and consistently, abrogated Warburg effect in cancer cells. Suppression of aerobic glycolysis by OA is mediated by PKM2/PKM1 switch. Furthermore, mTOR signaling was found to be inactivated in OA-treated cancer cells, and mTOR inhibition is required for the effect of OA on PKM2/PKM1 switch. Decreased expression of c-Myc-dependent hnRNPA1 and hnRNPA1 was responsible for OA-induced switch between PKM isoforms. Collectively, we identified that OA is an antitumor compound that suppresses aerobic glycolysis in cancer cells and there is potential that PKM2 may be developed as an important target in aerobic glycolysis pathway for developing novel anticancer agents.
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影响因子：
37.3
作者：
Iqbal MA;Siddiqui FA;Gupta V;Chattopadhyay S;Gopinath P;Kumar B;Manvati S;Chaman N;Bamezai RN
通讯作者：
Bamezai RN
DOI：
10.1073/pnas.1014769108
发表时间：
2011-03-08
影响因子：
11.1
作者：
Sun, Qian;Chen, Xinxin;Zhang, Hongbing
通讯作者：
Zhang, Hongbing
影响因子：
6.4
作者：
Vaughan, Roger A.;Garcia-Smith, Randi;Trujillo, Kristina A.
通讯作者：
Trujillo, Kristina A.
影响因子：
--
作者：
Cerella C;Radogna F;Dicato M;Diederich M
通讯作者：
Diederich M
影响因子：
5.1
作者：
Datta S;Li J;Mahdi F;Jekabsons MB;Nagle DG;Zhou YD
通讯作者：
Zhou YD