N-(1-Pyrenyl) maleimide inhibits telomerase activity in a cell free system and induces apoptosis in Jurkat cells.
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.
Department of Molecular and Cellular Biology, Chang Gung University, Kwei-San, Tao-Yuan, 333, Taiwan.
Pei-Rong
PR
Huang
Yuan-Ming
YM
Yeh
Chia-Chu
CC
Pao
Chi-Yuan
CY
Chen
Tzu-Chien V
TC
Wang
D017209:Apoptosis / Q000187:drug effects*; D002474:Cell-Free System; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D006801:Humans; D020128:Inhibitory Concentration 50; D019169:Jurkat Cells; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008301:Maleimides / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D019098:Telomerase / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D008301:Maleimides; C003944:N-(3-pyrene)maleimide; D019098:Telomerase