Department of Molecular and Cellular Biology, Chang Gung University, Kwei-San, Tao-Yuan, 333, Taiwan.
Mol Biol Rep. 2012 Sep;39(9):8899-905. doi: 10.1007/s11033-012-1757-y. Epub 2012 Jun 17.
Telomerase activity is repressed in normal human somatic cells, but is activated in most cancers, suggesting that telomerase may be an important target for cancer therapy. Agents that interact selectively with telomerase are anticipated to exert specific action on cancer cells. In this study, we evaluated maleimide derivatives for their potency and selectivity of telomerase inhibition. Among the several N-substituted derivatives of maleimide tested, N-(1-Pyrenyl) maleimide was shown to exert the greatest inhibition of telomerase in a cell free system, with an IC50 value of 0.25 μM. Importantly, we demonstrated that N-(1-pyrenyl) maleimide induces apoptosis in Jurkat T cells and displays the greatest differential cytotoxicity against hematopoietic cancer cells. These results suggest that N-(1-pyrenyl) maleimide is an attractive maleimide to be tested and developed as anti-cancer drug.
端粒酶活性在正常人体体细胞中受到抑制，但在大多数癌症中被激活，这表明端粒酶可能是癌症治疗的一个重要靶点。预计与端粒酶选择性相互作用的试剂将对癌细胞产生特异性作用。在这项研究中，我们评估了马来酰亚胺衍生物对端粒酶抑制的效力和选择性。在所测试的几种 N-取代的马来酰亚胺衍生物中，N-(1- 苊基)马来酰亚胺在无细胞体系中表现出最强的端粒酶抑制作用，IC50 值为 0.25 μM。重要的是，我们证明 N-(1- 苊基)马来酰亚胺诱导 Jurkat T 细胞凋亡，并对造血癌细胞显示出最大的差异细胞毒性。这些结果表明，N-(1- 苊基)马来酰亚胺是一种有吸引力的马来酰亚胺，可作为抗癌药物进行测试和开发。
