Synergistic anti-cancer effect of phenformin and oxamate.
Synergistic anti-cancer effect of phenformin and oxamate.
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DOI：
10.1371/journal.pone.0085576
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Choi JY
中科院分区：
文献类型：
--
作者：
Miskimins WK;Ahn HJ;Kim JY;Ryu S;Jung YS;Choi JY
苯乙双胍;一种抗糖尿病剂）加草氨酸盐[乳酸脱氢酶（LDH）抑制剂]作为潜在的抗癌治疗组合进行测试。在体外研究中，苯丙氨酸比二甲双胍更有效，二甲双胍是另一种双胍，最近被认为具有抗癌作用，在各种癌细胞系中促进癌细胞死亡25倍至1500万倍。苯丙氨酸的抗癌作用与线粒体中复合物I的抑制和随后的活性氧（ROS）的过度产生有关。添加草氨酸盐抑制细胞的LDH活性和乳酸盐产生，这是双胍的主要副作用，并通过减少ATP产生和加速ROS产生诱导更快速的癌细胞死亡。苯丙氨酸加草氨酸比苯丙氨酸加LDH敲低更有效。在同基因小鼠模型中，与对照组相比，苯丙氨酸与草氨酸盐增加了肿瘤细胞凋亡，减小了肿瘤大小和正电子发射断层扫描/计算机断层扫描上的18F-氟脱氧葡萄糖（FDG）摄取。我们的结论是，苯丙氨酸对癌细胞的细胞毒性比二甲双胍。此外，苯丙氨酸和草氨酸通过同时抑制线粒体中的复合物I和细胞质中的LDH而具有协同抗癌作用。
Phenformin (phenethylbiguanide; an anti-diabetic agent) plus oxamate [lactate dehydrogenase (LDH) inhibitor] was tested as a potential anti-cancer therapeutic combination. In in vitro studies, phenformin was more potent than metformin, another biguanide, recently recognized to have anti-cancer effects, in promoting cancer cell death in the range of 25 times to 15 million times in various cancer cell lines. The anti-cancer effect of phenformin was related to complex I inhibition in the mitochondria and subsequent overproduction of reactive oxygen species (ROS). Addition of oxamate inhibited LDH activity and lactate production by cells, which is a major side effect of biguanides, and induced more rapid cancer cell death by decreasing ATP production and accelerating ROS production. Phenformin plus oxamate was more effective than phenformin combined with LDH knockdown. In a syngeneic mouse model, phenformin with oxamate increased tumor apoptosis, reduced tumor size and 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography compared to control. We conclude that phenformin is more cytotoxic towards cancer cells than metformin. Furthermore, phenformin and oxamate have synergistic anti-cancer effects through simultaneous inhibition of complex I in the mitochondria and LDH in the cytosol, respectively.
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苯甲曲作为预防和乳腺癌异种移植的治疗。
影响因子：
8.8
作者：
Appleyard, M. V. C. L.;Murray, K. E.;Coates, P. J.;Wullschleger, S.;Bray, S. E.;Kernohan, N. M.;Fleming, S.;Alessi, D. R.;Thompson, A. M.
通讯作者：
Thompson, A. M.
影响因子：
11.2
作者：
Kisfalvi K;Eibl G;Sinnett-Smith J;Rozengurt E
通讯作者：
Rozengurt E
非小细胞肺癌组织中乳酸脱氢酶 5 (LDH-5) 过度表达与肿瘤缺氧、血管生成因子产生和不良预后有关。
影响因子：
8.8
作者：
Koukourakis, MI;Giatromanolaki, A;Sivridis, E;Bougioukas, G;Didilis, V;Gatter, KC;Harris, AL
通讯作者：
Harris, AL
影响因子：
5.2
作者：
Goetze, Kristina;Walenta, Stefan;Mueller-Klieser, Wolfgang
通讯作者：
Mueller-Klieser, Wolfgang
影响因子：
4.1
作者：
Blenn, Christian;Althaus, Felix R.;Malanga, Maria
通讯作者：
Malanga, Maria