Tumor necrosis factor alpha induces Warburg-like metabolism and is reversed by anti-inflammatory curcumin in breast epithelial cells
Tumor necrosis factor alpha induces Warburg-like metabolism and is reversed by anti-inflammatory curcumin in breast epithelial cells
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DOI：
10.1002/ijc.28264
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发表时间：
2013-11-15
影响因子：
6.4
通讯作者：
Trujillo, Kristina A.
中科院分区：
文献类型：
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作者：
Vaughan, Roger A.;Garcia-Smith, Randi;Trujillo, Kristina A.
癌细胞中细胞代谢的重新编程是一种有据可查的效应。此前已有研究表明，常见的癌基因表达可以诱导癌细胞中的有氧糖酵解。然而，炎症微环境对癌细胞代谢的直接影响尚不清楚。在这里，我们说明用低水平（10 ng/ml）肿瘤坏死因子α（TNF-）治疗非恶性（MCF-10a）和恶性（MCF-7）乳腺上皮细胞可显着增加糖酵解依赖性、乳酸输出和葡萄糖转运蛋白1（GLUT1）的表达。 TNF-减少线粒体总含量；然而，耗氧率没有显着改变，表明线粒体的整体功能有所增加。葡萄糖饥饿后，用 TNF-α 处理的 MCF7 细胞的活力明显低于未处理的细胞。有趣的是，这些特性可以通过与抗炎剂姜黄素以剂量依赖性方式共孵育来部分逆转。这项工作表明，有氧糖酵解可以由炎症微环境直接诱导，独立于额外的基因突变和来自邻近细胞的信号。此外，我们还发现天然膳食化合物可以逆转这种影响。
The reprogramming of cellular metabolism in cancer cells is a well-documented effect. It has previously been shown that common oncogene expression can induce aerobic glycolysis in cancer cells. However, the direct effect of an inflammatory microenvironment on cancer cell metabolism is not known. Here, we illustrate that treatment of nonmalignant (MCF-10a) and malignant (MCF-7) breast epithelial cells with low-level (10 ng/ml) tumor necrosis factor alpha (TNF-) significantly increased glycolytic reliance, lactate export and expression of the glucose transporter 1 (GLUT1). TNF- decreased total mitochondrial content; however, oxygen consumption rate was not significantly altered, suggesting that overall mitochondrial function was increased. Upon glucose starvation, MCF7 cells treated with TNF- demonstrated significantly lower viability than nontreated cells. Interestingly, these properties can be partially reversed by coincubation with the anti-inflammatory agent curcumin in a dose-dependent manner. This work demonstrates that aerobic glycolysis can be directly induced by an inflammatory microenvironment independent of additional genetic mutations and signals from adjacent cells. Furthermore, we have identified that a natural dietary compound can reverse this effect.