Laboratory of Tumour Cell Metabolism, Department of Cell and Developmental Biology, Biomedical Sciences Institute, University of São Paulo, Avenida Prof. Lineu Prestes 1524, CEP 05508-900, São Paulo, SP, Brazil.
Mol Neurobiol. 2010 Aug;42(1):76-88. doi: 10.1007/s12035-010-8134-4. Epub 2010 Apr 29.
Polyunsaturated fatty acids (PUFAs) are known to inhibit cell proliferation of many tumour types both in vitro and in vivo. Their capacity to interfere with cell proliferation has been linked to their induction of reactive oxygen species (ROS) production in tumour tissues leading to cell death through apoptosis. However, the exact mechanisms of action of PUFAs are far from clear, particularly in brain tumours. The loss of bound hexokinase from the mitochondrial voltage-dependent anion channel has been directly related to loss of protection from apoptosis, and PUFAs can induce this loss of bound hexokinase in tumour cells. Tumour cells overexpressing Akt activity, including gliomas, are sensitised to ROS damage by the Akt protein and may be good targets for chemotherapeutic agents, which produce ROS, such as PUFAs. Cardiolipin peroxidation may be an initial event in the release of cytochrome c from the mitochondria, and enriching cardiolipin with PUFA acyl chains may lead to increased peroxidation and therefore an increase in apoptosis. A better understanding of the metabolism of fatty acids and eicosanoids in primary brain tumours such as gliomas and their influence on energy balance will be fundamental to the possible targeting of mitochondria in tumour treatment.
多不饱和脂肪酸（PUFAs）已被证实能够在体外和体内抑制多种肿瘤类型的细胞增殖。其干扰细胞增殖的能力与其在肿瘤组织中诱导活性氧（ROS）产生有关，从而通过细胞凋亡导致细胞死亡。然而，PUFAs 的确切作用机制尚不清楚，特别是在脑肿瘤中。结合己糖激酶从线粒体电压依赖性阴离子通道的丢失与凋亡保护的丧失直接相关，PUFAs 可以诱导肿瘤细胞中结合己糖激酶的丢失。包括神经胶质瘤在内的过度表达 Akt 活性的肿瘤细胞对 Akt 蛋白引起的 ROS 损伤敏感，并且可能是产生 ROS 的化疗药物的良好靶点，例如 PUFAs。心磷脂过氧化可能是细胞色素 c 从线粒体中释放的初始事件，并且用 PUFAs 酰基链富集心磷脂可能导致过氧化增加，因此凋亡增加。更好地了解原发性脑肿瘤（如神经胶质瘤）中脂肪酸和类二十烷酸的代谢及其对能量平衡的影响，将是肿瘤治疗中靶向线粒体的基础。
