细胞凋亡
细胞色素c
线粒体
活性氧
生物化学
碎片(计算)
生物
DNA断裂
脂质过氧化
细胞生物学
二十碳五烯酸
脂质代谢
化学
多不饱和脂肪酸
程序性细胞死亡
脂肪酸
氧化应激
生态学
作者
Alison Colquhoun,Robert I. Schumacher
标识
DOI:10.1016/s1388-1981(01)00136-6
摘要
The polyunsaturated fatty acids gamma-linolenic acid (GLA) and eicosapentaenoic acid (EPA) are cytotoxic to tumour cells. GLA inhibits Walker 256 tumour growth in vivo, causing alterations in mitochondrial ultrastructure and cellular metabolism. The objective of the present study was to investigate the mechanisms behind fatty acid inhibition of Walker 256 tumour growth under controlled in vitro conditions. At a concentration of 150 microM, both GLA and EPA caused a decrease in cell proliferation and an increase in apoptotic index. Increases in reactive oxygen species (ROS) and lipid peroxide production were identified, as well as alterations in energy metabolism and the deposition of large amounts of triacylglycerol in the form of lipid droplets. Mitochondrial respiratory chain complexes I+III and IV had significantly decreased activity and mitochondrial membrane potential was greatly diminished. Intracellular ATP concentrations were maintained at 70-80% of control values despite the decreased mitochondrial function, which may be in part due to increased utilisation of glucose for ATP generation. Cytochrome c release from mitochondria was found, as was caspase-3-like activation. DNA fragmentation in situ revealed many apoptotic events within the cell population. The mechanism(s) by which ROS and lipid peroxides induce apoptosis remains unclear, but the effects of GLA and EPA appear to involve the mitochondrial pathway of apoptosis induction leading to cytochrome c release, caspase activation, loss of mitochondrial membrane potential and DNA fragmentation.
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