Floridi A, Castiglione S, Bianchi C, Mancini A
Laboratory of Cell Metabolism and Pharmacokinetics, Regina Elena Institute for Cancer Research, Rome, Italy.
Biochem Pharmacol. 1990 Jul 15;40(2):217-22. doi: 10.1016/0006-2952(90)90681-a.
The effect of rhein, 4,5-dihydroxyanthraquinone-2-carboxylic acid, on oxygen consumption and the rate of aerobic and anaerobic lactate production by Ehrlich ascites tumor cells has been investigated. The rate of oxygen uptake decreases with the increase of rhein concentration. Rhein also inhibits aerobic and anaerobic glycolysis. The rate of aerobic lactate production decreases with the drug concentration and the maximal effect was observed at 0.100 mM. Anaerobic lactate production is also inhibited and the maximum effect is reached at 0.220 mM. The possibility that the lactate production decrease was secondary to an effect on mitochondrial ATPase was excluded on the basis of the data with DNP and oligomycin. Rhein reduces the intracellular level of lactate, pyruvate and glucose-6-phosphate. Glucose utilization and 2-deoxy-D-glucose uptake are decreased to the same extent as the inhibition of aerobic lactate production, whereas glucose phosphorylation is unaffected. It is, therefore, concluded that the inhibition of glycolysis of Ehrlich ascites tumor cells by rhein is caused by an impairment of glucose uptake.
研究了大黄酸(4,5 - 二羟基蒽醌 - 2 - 羧酸)对艾氏腹水癌细胞耗氧量以及有氧和无氧乳酸生成速率的影响。耗氧速率随大黄酸浓度的增加而降低。大黄酸还抑制有氧和无氧糖酵解。有氧乳酸生成速率随药物浓度降低,在0.100 mM时观察到最大效应。无氧乳酸生成也受到抑制,在0.220 mM时达到最大效应。基于二硝基苯酚(DNP)和寡霉素的数据排除了乳酸生成减少是由于对线粒体ATP酶产生影响的可能性。大黄酸降低了细胞内乳酸、丙酮酸和6 - 磷酸葡萄糖的水平。葡萄糖利用和2 - 脱氧 - D - 葡萄糖摄取的减少程度与有氧乳酸生成的抑制程度相同,而葡萄糖磷酸化不受影响。因此,得出结论,大黄酸对艾氏腹水癌细胞糖酵解的抑制是由葡萄糖摄取受损引起的。