Castiglione S, Fanciulli M, Bruno T, Evangelista M, Del Carlo C, Paggi M G, Chersi A, Floridi A
Laboratory for Cell Metabolism and Pharmacokinetics, Regina Elena Institute for Cancer Research, Rome, Italy.
Anticancer Drugs. 1993 Jun;4(3):407-14. doi: 10.1097/00001813-199306000-00019.
Rhein (RH), 4,5 dihydroxyanthraquinone-2-carboxylic acid, is known to inhibit the glycolysis of neoplastic cells by impairing glucose uptake. In order to establish whether this might be due to a selective interaction of the carrier with the drug or to functional modifications of the cell membrane, the effect of RH on glucose uptake in Ehrlich ascites tumor cells has been investigated. RH strongly inhibits the uptake of both 2-deoxyglucose and 3-O-methylglucose, so the reduced influx therefore cannot be ascribed to an effect on glucose phosphorylation. The inhibition of glucose transport does not depend on a reduction of the number of the carriers as indicated by the inability of the drug to interfere with the synthesis of the transporter. Moreover, the extent of total binding of cytochalasin B, as well as the fact that glucose specificity is not altered, indicate that the intrinsic activity of the glucose carrier is not affected. We therefore conclude that the inhibition of glucose uptake must be ascribed to an interaction of the drug with cell membranes that results in an alteration of membrane-associated functions.
大黄酸（RH），即4,5-二羟基蒽醌-2-羧酸，已知可通过损害葡萄糖摄取来抑制肿瘤细胞的糖酵解。为了确定这是否可能是由于载体与药物的选择性相互作用或细胞膜的功能改变所致，研究了RH对艾氏腹水瘤细胞葡萄糖摄取的影响。RH强烈抑制2-脱氧葡萄糖和3-O-甲基葡萄糖的摄取，因此，流入减少不能归因于对葡萄糖磷酸化的影响。葡萄糖转运的抑制并不取决于载体数量的减少，这一点由药物无法干扰转运蛋白的合成所表明。此外，细胞松弛素B的总结合程度以及葡萄糖特异性未改变这一事实表明，葡萄糖载体的内在活性不受影响。因此，我们得出结论，葡萄糖摄取的抑制必须归因于药物与细胞膜的相互作用，这种相互作用导致膜相关功能的改变。
