Resveratrol inhibits cancer cell metabolism by down regulating pyruvate kinase M2 via inhibition of mammalian target of rapamycin.
Resveratrol inhibits cancer cell metabolism by down regulating pyruvate kinase M2 via inhibition of mammalian target of rapamycin.
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DOI：
10.1371/journal.pone.0036764
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Bamezai RN
中科院分区：
文献类型：
--
作者：
Iqbal MA;Bamezai RN
以丙酮酸激酶M2（PKM 2）为中心的癌细胞代谢在近年来的癌症研究中具有重要意义。以葡萄糖摄取增强、乳酸盐和葡萄糖生成为特征的癌细胞代谢被认为是治疗干预的理想靶点。PKM 2的表达有利于癌细胞的代谢，因此，本研究旨在研究迄今为止未知的植物抗毒素白藜芦醇对PKM 2表达的影响及其对癌症代谢的影响。我们观察到白藜芦醇通过抑制mTOR信号传导来下调PKM 2表达，并通过减少葡萄糖摄入、乳酸产生（有氧糖酵解）和减少各种癌细胞系中的合成代谢（大分子合成）来抑制癌症代谢。核糖-5-磷酸（R5 P），戊糖磷酸途径的关键中间体，细胞内水平的偶然下降，占减少的抗氧化剂。因此，抑制癌症代谢的状态导致细胞增殖减少。有趣的是，shRNA介导的PKM 2沉默抑制葡萄糖摄取和乳酸产生，为PKM 2的关键作用及其介导白藜芦醇对癌症代谢的影响提供了证据。此外，PKM 2的过度表达消除了白藜芦醇的观察到的效果，这表明PKM 2下调作为白藜芦醇的关键功能的作用。该研究报告了白藜芦醇对癌症代谢的新型PKM 2介导的作用，并为其治疗潜力提供了新的维度。
Metabolism of cancer cells with pyruvate kinase M2 (PKM2) at its centre stage has assumed a prime significance in cancer research in recent times. Cancer cell metabolism, characterized by enhanced glucose uptake, production of lactate and anabolism is considered an ideal target for therapeutic interventions. Expression of PKM2 switches metabolism in favor of cancer cells, therefore, the present study was designed to investigate the hitherto unknown effect of resveratrol, a phytoalexin, on PKM2 expression and resultant implications on cancer metabolism. We observed that resveratrol down-regulated PKM2 expression by inhibiting mTOR signaling and suppressed cancer metabolism, adjudged by decreased glucose uptake, lactate production (aerobic glycolysis) and reduced anabolism (macromolecule synthesis) in various cancer cell lines. A contingent decrease in intracellular levels of ribose-5-phosphate (R5P), a critical intermediate of pentose phosphate pathway, accounted for a reduced anabolism. Consequently, the state of suppressed cancer metabolism resulted in decreased cellular proliferation. Interestingly, shRNA-mediated silencing of PKM2 inhibited glucose uptake and lactate production, providing evidence for the critical role of PKM2 and its mediation in the observed effects of resveratrol on cancer metabolism. Further, an over-expression of PKM2 abolished the observed effects of resveratrol, signifying the role of PKM2 downregulation as a critical function of resveratrol. The study reports a novel PKM2-mediated effect of resveratrol on cancer metabolism and provides a new dimension to its therapeutic potential.
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影响因子：
8.8
作者：
通讯作者：
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影响因子：
3.9
作者：
KAYNE, FJ;PRICE, NC
通讯作者：
PRICE, NC
影响因子：
7.5
作者：
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通讯作者：
Sabatini DM
影响因子：
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作者：
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通讯作者：
Bernard-Gallon, DJ
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82.9
作者：
Majumder, PK;Febbo, PG;Sellers, WR
通讯作者：
Sellers, WR