The HK2 Dependent "Warburg Effect" and Mitochondrial Oxidative Phosphorylation in Cancer: Targets for Effective Therapy with 3-Bromopyruvate.
The HK2 Dependent "Warburg Effect" and Mitochondrial Oxidative Phosphorylation in Cancer: Targets for Effective Therapy with 3-Bromopyruvate.
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DOI：
10.3390/molecules21121730
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发表时间：
2016-12-15
期刊：
影响因子：
--
通讯作者：
Ułaszewski S
中科院分区：
文献类型：
--
作者：
Lis P;Dyląg M;Niedźwiecka K;Ko YH;Pedersen PL;Goffeau A;Ułaszewski S
本文综述了目前关于癌细胞代谢的知识，特别是关于“瓦尔堡”和“克拉布特里”效应。这项工作还总结了两个关键发现，其中之一涉及己糖激酶-2（HK 2），它是“瓦尔堡效应”和癌细胞永生化的主要参与者。第二个发现与以下发现有关：癌细胞与正常细胞不同，其多达60%的ATP通过“瓦尔堡效应”从糖酵解中获得，其余40%来自线粒体氧化磷酸化。还描述了通常在癌细胞内充当强能量阻断剂的所选抗癌剂。其中，3-溴丙酮酸（3BP）是研究的热点。这种小的烷基化化合物靶向“瓦尔堡效应”，即，甚至在氧存在下糖酵解的升高，以及癌细胞中的线粒体氧化磷酸化。正常细胞不会受到伤害。3BP可迅速杀死组织培养中生长的癌细胞，根除动物肿瘤，并防止转移。此外，适当配制的3BP也显示出作为人类有效抗肝癌剂的前景，并且对称为“多发性骨髓瘤”的癌症也有效。最后，3BP已经被证明可以显著延长没有其他选择的人类患者的生命。因此，可以说，3BP是一个非常有前途的新的抗癌剂在进行临床开发的过程中。
This review summarizes the current state of knowledge about the metabolism of cancer cells, especially with respect to the “Warburg” and “Crabtree” effects. This work also summarizes two key discoveries, one of which relates to hexokinase-2 (HK2), a major player in both the “Warburg effect” and cancer cell immortalization. The second discovery relates to the finding that cancer cells, unlike normal cells, derive as much as 60% of their ATP from glycolysis via the “Warburg effect”, and the remaining 40% is derived from mitochondrial oxidative phosphorylation. Also described are selected anticancer agents which generally act as strong energy blockers inside cancer cells. Among them, much attention has focused on 3-bromopyruvate (3BP). This small alkylating compound targets both the “Warburg effect”, i.e., elevated glycolysis even in the presence oxygen, as well as mitochondrial oxidative phosphorylation in cancer cells. Normal cells remain unharmed. 3BP rapidly kills cancer cells growing in tissue culture, eradicates tumors in animals, and prevents metastasis. In addition, properly formulated 3BP shows promise also as an effective anti-liver cancer agent in humans and is effective also toward cancers known as “multiple myeloma”. Finally, 3BP has been shown to significantly extend the life of a human patient for which no other options were available. Thus, it can be stated that 3BP is a very promising new anti-cancer agent in the process of undergoing clinical development.
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影响因子：
8
作者：
Gandham SK;Talekar M;Singh A;Amiji MM
通讯作者：
Amiji MM
影响因子：
4.1
作者：
Crabtree, HG
通讯作者：
Crabtree, HG
DOI：
10.1073/pnas.74.9.3735
发表时间：
1977-01-01
影响因子：
11.1
作者：
BUSTAMANTE, E;PEDERSEN, PL
通讯作者：
PEDERSEN, PL
影响因子：
3.1
作者：
Gupta, Vibhor;Wellen, Kathryn E.;Bamezai, Rameshwar N. K.
通讯作者：
Bamezai, Rameshwar N. K.
影响因子：
8
作者：
DeBerardinis, R. J.;Cheng, T.
通讯作者：
Cheng, T.