Eugenol inhibits oxidative phosphorylation and fatty acid oxidation via downregulation of c-Myc/PGC-1β/ERRα signaling pathway in MCF10A-ras cells.
Eugenol inhibits oxidative phosphorylation and fatty acid oxidation via downregulation of c-Myc/PGC-1β/ERRα signaling pathway in MCF10A-ras cells.
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丁子香酚通过下调 MCF10A-ras 细胞中的 c-Myc/PGC-1 beta/ERRa 信号通路抑制氧化磷酸化和脂肪酸氧化
DOI：
10.1038/s41598-017-13505-x
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发表时间：
2017-10-10
影响因子：
4.6
通讯作者：
Jiang X
中科院分区：
文献类型：
--
作者：
Yan X;Zhang G;Bie F;Lv Y;Ma Y;Ma M;Wang Y;Hao X;Yuan N;Jiang X
细胞能量代谢的改变在癌症的发生和发展中起着关键作用。针对癌症治疗的代谢途径已被研究为潜在的预防或治疗方法。丁香酚（Eugenol，Eu）是丁香属植物丁香精油的主要挥发性成分，是一种潜在的化学预防药物。然而，Eu调节细胞能量代谢的机制仍然没有很好的定义。本研究旨在确定Eu对细胞能量代谢的影响，在早期癌症的进展，采用未转化和H-ras癌基因转染的MCF 10A人乳腺上皮细胞。Eu对MCF 10A-ras细胞有剂量依赖性的选择性杀伤作用，但对MCF 10A细胞无明显杀伤作用。Eu处理也显着降低MCF 10A-ras细胞内ATP水平，但在MCF 10A细胞中没有。这种作用主要是通过下调MCF 10A-ras细胞c-Myc/PGC-1β/ERRα信号通路，抑制氧化磷酸化（OXPHOS）复合物和脂肪酸氧化（FAO）蛋白（包括PPARα、MCAD和CPT 1C）的表达，减轻氧化应激而实现的。这些结果表明，一种新的机制，涉及调节细胞的能量代谢，Eu可能会阻止乳腺癌的进展。
Alteration in cellular energy metabolism plays a critical role in the development and progression of cancer. Targeting metabolic pathways for cancer treatment has been investigated as potential preventive or therapeutic methods. Eugenol (Eu), a major volatile constituent of clove essential oil mainly obtained from Syzygium, has been reported as a potential chemopreventive drug. However, the mechanism by which Eu regulates cellular energy metabolism is still not well defined. This study was designed to determine the effect of Eu on cellular energy metabolism during early cancer progression employing untransformed and H-ras oncogene transfected MCF10A human breast epithelial cells. Eu showed dose-dependent selective cytotoxicity toward MCF10A-ras cells but exhibited no apparent cytotoxicity in MCF10A cells. Treatment with Eu also significantly reduced intracellular ATP levels in MCF10A-ras cells but not in MCF10A cells. This effect was mediated mainly through inhibiting oxidative phosphorylation (OXPHOS) complexs and the expression of fatty acid oxidation (FAO) proteins including PPARα, MCAD and CPT1C by downregulating c-Myc/PGC-1β/ERRα pathway and decreasing oxidative stress in MCF10A-ras cells. These results indicate a novel mechanism involving the regulation of cellular energy metabolism by which Eu may prevent breast cancer progression.
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影响因子：
--
作者：
Balaban S;Lee LS;Schreuder M;Hoy AJ
通讯作者：
Hoy AJ
美烯醇诱导的癌细胞凋亡的抗增生性和分子机制。
DOI：
10.3390/molecules17066290
发表时间：
2012-05-25
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Jaganathan SK;Supriyanto E
通讯作者：
Supriyanto E
影响因子：
3.7
作者：
Kadota M;Yang HH;Gomez B;Sato M;Clifford RJ;Meerzaman D;Dunn BK;Wakefield LM;Lee MP
通讯作者：
Lee MP
影响因子：
9
作者：
BLAND, KI;KONSTADOULAKIS, MM;WANEBO, HJ
通讯作者：
WANEBO, HJ
影响因子：
254.7
作者：
DeSantis, Carol E.;Fedewa, Stacey A.;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin