Diomede L, Bizzi A, Magistrelli A, Modest E J, Salmona M, Noseda A
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Int J Cancer. 1990 Aug 15;46(2):341-6. doi: 10.1002/ijc.2910460234.
Membrane-interactive ether lipids (EL) exert toxic and antiproliferative effects on cancer cells in vitro. They appear to be selectively more toxic to cancer cells than to normal cells and thus they are ideal candidates for bone-marrow purging procedures. However, no conclusive explanation has yet been provided for this property. We now present some data indicating that the cholesterol concentration in the incubation medium modulates EL toxicity against the HL60 leukemic cell line in vitro. Furthermore, model membranes richer in cholesterol take up EL more slowly, and cell cholesterol enrichment of HL60 cells counteracts EL biophysical membrane interaction, but not toxicity, in our experimental model. However, the K562 cell line, a leukemia line less sensitive to EL toxic action, has higher levels of cell cholesterol. Our data provide evidence to explain differences in sensitivity to EL among different cell types and contribute to the understanding of the mechanism of action of EL.
膜相互作用醚脂（EL）在体外对癌细胞具有毒性和抗增殖作用。它们似乎对癌细胞的选择性毒性高于正常细胞，因此是骨髓净化程序的理想候选物。然而，尚未对这种特性给出确凿的解释。我们现在提供一些数据，表明孵育培养基中的胆固醇浓度在体外调节EL对HL60白血病细胞系的毒性。此外，富含胆固醇的模型膜摄取EL的速度更慢，并且在我们的实验模型中，HL60细胞的细胞胆固醇富集抵消了EL与生物物理膜的相互作用，但没有抵消毒性。然而，K562细胞系是一种对EL毒性作用不太敏感的白血病细胞系，其细胞胆固醇水平较高。我们的数据为解释不同细胞类型对EL敏感性的差异提供了证据，并有助于理解EL的作用机制。
