Matcha green tea (MGT) inhibits the propagation of cancer stem cells (CSCs), by targeting mitochondrial metabolism, glycolysis and multiple cell signalling pathways.
Matcha green tea (MGT) inhibits the propagation of cancer stem cells (CSCs), by targeting mitochondrial metabolism, glycolysis and multiple cell signalling pathways.
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DOI：
10.18632/aging.101483
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发表时间：
2018-08-23
期刊：
影响因子：
--
通讯作者：
Lisanti MP
中科院分区：
文献类型：
--
作者：
Bonuccelli G;Sotgia F;Lisanti MP
抹茶绿色茶（MGT）是一种天然产品，目前被用作膳食补充剂，可能具有显着的抗癌特性。然而，支持其潜在健康益处的分子机制在很大程度上仍然未知。在这里，我们使用MCF 7细胞（ER（+）人乳腺癌细胞系）作为模型系统，通过i）代谢表型分析和ii）无偏蛋白质组学分析，系统地剖析MGT在细胞水平上的作用。我们的研究结果表明，MGT确实足以抑制乳腺癌干细胞（CSC）的增殖，IC-50约为0.2 mg/ml，在组织培养。有趣的是，代谢表型分析显示，用MGT治疗足以抑制氧化线粒体代谢（OXPHOS）和糖酵解通量，使癌细胞转向更静止的代谢状态。无偏无标记蛋白质组学分析确定了特定的线粒体蛋白质和糖酵解酶，MGT治疗下调。此外，为了发现参与这种代谢转变的潜在信号传导途径，我们通过Influencity Pathway Analysis（IPA）软件对蛋白质组学数据集进行了生物信息学询问。我们的研究结果表明，MGT强烈影响mTOR信号转导，特别是下调40 S核糖体的许多成分。这提出了一种有趣的可能性，即MGT可以用作mTOR的抑制剂，而不是化学化合物，如雷帕霉素。此外，其他关键途径也受到影响，包括抗氧化反应、细胞周期调节以及白细胞介素信号传导。我们的研究结果与MGT通过介导癌细胞的代谢重编程可能具有显著治疗潜力的想法一致。
Matcha green tea (MGT) is a natural product that is currently used as a dietary supplement and may have significant anti-cancer properties. However, the molecular mechanism(s) underpinning its potential health benefits remain largely unknown. Here, we used MCF7 cells (an ER(+) human breast cancer cell line) as a model system, to systematically dissect the effects of MGT at the cellular level, via i) metabolic phenotyping and ii) unbiased proteomics analysis. Our results indicate that MGT is indeed sufficient to inhibit the propagation of breast cancer stem cells (CSCs), with an IC-50 of ~0.2 mg/ml, in tissue culture. Interestingly, metabolic phenotyping revealed that treatment with MGT is sufficient to suppress both oxidative mitochondrial metabolism (OXPHOS) and glycolytic flux, shifting cancer cells towards a more quiescent metabolic state. Unbiased label-free proteomics analysis identified the specific mitochondrial proteins and glycolytic enzymes that were down-regulated by MGT treatment. Moreover, to discover the underlying signalling pathways involved in this metabolic shift, we subjected our proteomics data sets to bio-informatics interrogation via Ingenuity Pathway Analysis (IPA) software. Our results indicate that MGT strongly affected mTOR signalling, specifically down-regulating many components of the 40S ribosome. This raises the intriguing possibility that MGT can be used as inhibitor of mTOR, instead of chemical compounds, such as rapamycin. In addition, other key pathways were affected, including the anti-oxidant response, cell cycle regulation, as well as interleukin signalling. Our results are consistent with the idea that MGT may have significant therapeutic potential, by mediating the metabolic reprogramming of cancer cells.
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影响因子：
4.6
作者：
Kumazoe M;Takai M;Hiroi S;Takeuchi C;Yamanouchi M;Nojiri T;Onda H;Bae J;Huang Y;Takamatsu K;Yamashita S;Yamada S;Kangawa K;Takahashi T;Tanaka H;Tachibana H
通讯作者：
Tachibana H
影响因子：
3.9
作者：
Lambert JD;Elias RJ
通讯作者：
Elias RJ
影响因子：
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作者：
Lamb R;Fiorillo M;Chadwick A;Ozsvari B;Reeves KJ;Smith DL;Clarke RB;Howell SJ;Cappello AR;Martinez-Outschoorn UE;Peiris-Pagès M;Sotgia F;Lisanti MP
通讯作者：
Lisanti MP
影响因子：
--
作者：
Lamb R;Ozsvari B;Lisanti CL;Tanowitz HB;Howell A;Martinez-Outschoorn UE;Sotgia F;Lisanti MP
通讯作者：
Lisanti MP
影响因子：
3.8
作者：
Jang JY;Lee JK;Jeon YK;Kim CW
通讯作者：
Kim CW