Effect of mitochondrial uncouplers niclosamide ethanolamine (NEN) and oxyclozanide on hepatic metastasis of colon cancer.
Effect of mitochondrial uncouplers niclosamide ethanolamine (NEN) and oxyclozanide on hepatic metastasis of colon cancer.
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DOI：
10.1038/s41419-017-0092-6
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发表时间：
2018-02-13
影响因子：
9
通讯作者：
Jin S
中科院分区：
文献类型：
--
作者：
Alasadi A;Chen M;Swapna GVT;Tao H;Guo J;Collantes J;Fadhil N;Montelione GT;Jin S
癌细胞的代谢是有氧糖酵解的特征，或者有氧糖酵解的糖化效果将丙酮酸液化降低到线粒体中，以防止葡萄糖的氧化，并使葡萄糖的氧化为何种策略，以使葡萄糖的生效效果。因为它的潜在抗癌活性。在不产生ATP的情况下促进质子在线粒体内部膜的影响，刺激乙酰基氧化的徒劳周期。在结肠癌MC38细胞中的葡萄糖代谢使用代谢组NMR方法，我们证明了线粒体解偶联的影响会促进丙酮酸对线粒体的影响，并降低各种合成途径的活性。线粒体解耦合减少了APCMIN/+小鼠中的肠道息肉，并减少了在胞内移植的结肠癌细胞的肝转移。
Metabolism of cancer cells is characterized by aerobic glycolysis, or the Warburg effect. Aerobic glycolysis reduces pyruvate flux into mitochondria, preventing a complete oxidation of glucose and shunting glucose to anabolic pathways essential for cell proliferation. Here we tested a new strategy, mitochondrial uncoupling, for its potential of antagonizing the anabolic effect of aerobic glycolysis and for its potential anticancer activities. Mitochondrial uncoupling is a process that facilitates proton influx across the mitochondrial inner membrane without generating ATP, stimulating a futile cycle of acetyl- CoA oxidation. We tested two safe mitochondrial uncouplers, NEN (niclosamide ethanolamine) and oxyclozanide, on their metabolic effects and anti-cancer activities. We used metabolomic NMR to examine the effect of mitochondrial uncoupling on glucose metabolism in colon cancer MC38 cells. We further tested the anti-cancer effect of NEN and oxyclozanide in cultured cell models, APCmin/+ mouse model, and a metastatic colon cancer mouse model. Using a metabolomic NMR approach, we demonstrated that mitochondrial uncoupling promotes pyruvate influx to mitochondria and reduces various anabolic pathway activities. Moreover, mitochondrial uncoupling inhibits cell proliferation and reduces clonogenicity of cultured colon cancer cells. Furthermore, oral treatment with mitochondrial uncouplers reduces intestinal polyp formation in APCmin/+ mice, and diminishes hepatic metastasis of colon cancer cells transplanted intrasplenically. Our data highlight a unique approach for targeting cancer cell metabolism for cancer prevention and treatment, identified two prototype compounds, and shed light on the anti-cancer mechanism of niclosamide.
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影响因子：
5.7
作者：
Londoño-Joshi AI;Arend RC;Aristizabal L;Lu W;Samant RS;Metge BJ;Hidalgo B;Grizzle WE;Conner M;Forero-Torres A;Lobuglio AF;Li Y;Buchsbaum DJ
通讯作者：
Buchsbaum DJ
DOI：
10.1046/j.1467-789x.2001.00043.x
发表时间：
2001-11-01
期刊：
Obesity reviews : an official journal of the International Association for the Study of Obesity
影响因子：
--
作者：
Harper, J A;Dickinson, K;Brand, M D
通讯作者：
Brand, M D
影响因子：
6.4
作者：
Jastroch M;Divakaruni AS;Mookerjee S;Treberg JR;Brand MD
通讯作者：
Brand MD
DOI：
10.1002/pros.23015
发表时间：
2015-09
期刊：
The Prostate
影响因子：
--
作者：
Liu C;Lou W;Armstrong C;Zhu Y;Evans CP;Gao AC
通讯作者：
Gao AC
影响因子：
11.2
作者：
Jin, Yanli;Lu, Zhongzheng;Pan, Jingxuan
通讯作者：
Pan, Jingxuan