Brunner G, Zalkow L, Burgess E, Rifkin D B, Wilson E L, Gruszecka-Kowalik E, Powis G
Department of Cell Biology, New York University Medical School, New York, USA.
Anticancer Res. 1996 Sep-Oct;16(5A):2513-6.
A number of proteins are found attached to the plasma membrane of mammalian cells by a glycosylphosphatidylinositol (GPI) anchor that can be cleaved by GPI specific phospholipase D (GPI-PLD). There are no known specific inhibitors of GPI-PLD. We examined some inhibitors of phosphatidylinositol specific phospholipase C (PI-PLC) for their ability to inhibit human serum and human bone marrow cell GPI-PLD. Azo analogues of suramin were found to be potent inhibitors of GPI-PLD. One compound had an IC50 of 3.7 microM that was 10-fold lower than the IC50 required to inhibit PI-PLC. The azo suramin analogues inhibited cancer cell growth at concentrations similar to those required to inhibit GPI-PLD, and below concentrations required to inhibit growth factor binding. It is possible that inhibition of cell growth might be related to the ability of the compounds to inhibit GPI-PLD.
许多蛋白质通过糖基磷脂酰肌醇（GPI）锚定在哺乳动物细胞的质膜上，该锚定可被GPI特异性磷脂酶D（GPI-PLD）切割。目前尚无已知的GPI-PLD特异性抑制剂。我们研究了一些磷脂酰肌醇特异性磷脂酶C（PI-PLC）抑制剂抑制人血清和人骨髓细胞GPI-PLD的能力。发现苏拉明的偶氮类似物是GPI-PLD的有效抑制剂。一种化合物的IC50为3.7 microM，比抑制PI-PLC所需的IC50低10倍。偶氮苏拉明类似物在与抑制GPI-PLD所需浓度相似的浓度下抑制癌细胞生长，且低于抑制生长因子结合所需的浓度。细胞生长的抑制可能与这些化合物抑制GPI-PLD的能力有关。
