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首页> 外文期刊>Molecules >The HK2 Dependent 'Warburg Effect' and Mitochondrial Oxidative Phosphorylation in Cancer: Targets for Effective Therapy with 3-Bromopyruvate
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The HK2 Dependent 'Warburg Effect' and Mitochondrial Oxidative Phosphorylation in Cancer: Targets for Effective Therapy with 3-Bromopyruvate

机译：HK2依赖的“ Warburg效应”和线粒体氧化磷酸化在癌症：3-溴丙酮酸有效治疗的目标。

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摘要

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.
机译：这篇综述总结了关于癌细胞代谢的知识的现状，尤其是关于“ Warburg”和“ Crabtree”效应的知识。这项工作还总结了两个关键发现，其中之一与己糖激酶-2（HK2）有关，后者是“ Warburg效应”和癌细胞永生化的主要参与者。第二个发现与发现癌细胞不同，癌细胞不同于正常细胞，是通过“ Warburg效应”从糖酵解中获得多达60％的ATP，其余40％来自线粒体的氧化磷酸化。还描述了选择的抗癌剂，其通常在癌细胞内充当强能量阻断剂。其中，许多注意力集中在3-溴丙酮酸（3BP）上。这种小的烷基化化合物既靶向“ Warburg效应”，即即使在存在氧气的情况下糖酵解也增强，并且靶向癌细胞中的线粒体氧化磷酸化。正常细胞仍未受损。 3BP可迅速杀死组织培养物中生长的癌细胞，根除动物体内的肿瘤并防止转移。另外，适当配制的3BP也显示出作为人类有效的抗肝癌剂的希望，并且对称为“多发性骨髓瘤”的癌症也有效。最后，已证明3BP可以显着延长人类患者的寿命，而其他方法均无法使用。因此，可以说3BP是在临床开发过程中非常有前途的新型抗癌剂。

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