Inhibition of the Warburg effect with a natural compound reveals a novel measurement for determining the metastatic potential of breast cancers.
Inhibition of the Warburg effect with a natural compound reveals a novel measurement for determining the metastatic potential of breast cancers.
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DOI：
10.18632/oncotarget.2689
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发表时间：
2015-01-20
期刊：
影响因子：
--
通讯作者：
Dean-Colomb W
中科院分区：
文献类型：
--
作者：
Arora R;Schmitt D;Karanam B;Tan M;Yates C;Dean-Colomb W
代谢是癌细胞的重要分化特征。乳酸脱氢酶（LDH）A/B是代谢上重要的蛋白质，并且参与乳酸向丙酮酸的相互转化的关键步骤。Panepoxydone（PP）是一种天然NF-kB抑制剂，可显著降低MCF-7和三阴性（MDA-MB-231、MDA-MB-468和MDA-MB-453）乳腺癌细胞的耗氧量和乳酸盐产生。流式细胞仪进一步观察到PP抑制线粒体膜电位和ATP合成。PP还上调LDH-B和下调LDH-A在所有乳腺癌细胞中的表达水平，与在HMEC细胞中观察到的水平相似。LDH-B在癌细胞系中的过度表达导致细胞凋亡增强、线粒体损伤和细胞迁移减少。分析GEO网站上可获得的患者数据集GDS 4069，我们观察到100%的非TNBC和60%的TNBC患者的LDH-B表达水平低于LDH-A表达水平。在此，我们报告了一个新的术语称为糖酵解指数，一种新的方法来计算利用氧化磷酸化在乳腺癌细胞通过测量LDH-B的LDH-A的比例。此外，NF-kB的抑制剂可以用作靶向代谢和用于治疗三阴性乳腺癌的治疗剂。
Metabolism is an important differentiating feature of cancer cells. Lactate dehydrogenases (LDH) A/B are metabolically important proteins and are involved in the critical step of inter-conversion of lactate to pyruvate. Panepoxydone (PP), a natural NF-kB inhibitor, significantly reduces the oxygen consumption and lactate production of MCF-7 and triple negative (MDA-MB-231, MDA-MB-468 and MDA-MB-453) breast cancer cells. We further observed that PP inhibited mitochondrial membrane potential and the ATP synthesis using flow cytometry. PP also up-regulated LDH-B and down-regulated LDH-A expression levels in all breast cancer cells to similar levels observed in HMEC cells. Over-expression of LDH-B in cancer cell lines leads to enhanced apoptosis, mitochondrial damage, and reduced cell migration. Analyzing the patient data set GDS4069 available on the GEO website, we observed 100% of non TNBC and 60% of TNBC patients had less LDH-B expression than LDH-A expression levels. Herein we report a new term called Glycolytic index, a novel method to calculate utilization of oxidative phosphorylation in breast cancer cells through measuring the ratio of the LDH-B to LDH-A. Furthermore, inhibitors of NF-kB could serve as a therapeutic agent for targeting metabolism and for the treatment of triple negative breast cancer.
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DOI：
10.1158/1078-0432.ccr-13-0623
发表时间：
2013-07-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Dennison JB;Molina JR;Mitra S;González-Angulo AM;Balko JM;Kuba MG;Sanders ME;Pinto JA;Gómez HL;Arteaga CL;Brown RE;Mills GB
通讯作者：
Mills GB
影响因子：
8
作者：
Leiblich, A.;Cross, S. S.;Rehman, I.
通讯作者：
Rehman, I.
影响因子：
64.5
作者：
Hsu, Peggy P.;Sabatini, David M.
通讯作者：
Sabatini, David M.
影响因子：
56.9
作者：
MARKERT, CL
通讯作者：
MARKERT, CL
影响因子：
3.7
作者：
Arora R;Yates C;Gary BD;McClellan S;Tan M;Xi Y;Reed E;Piazza GA;Owen LB;Dean-Colomb W
通讯作者：
Dean-Colomb W