Abstract
In a search for anticancer drugs by screening for inhibitors of telomerase, we have identified several small-molecule inhibitors that selectively inhibit telomerase in a cell-free system. Among these inhibitors, N-(1-pyrenyl) maleimide (NPM) induced apoptosis and displayed the greatest differential cytotoxicity against acute T cell leukemia-derived Jurkat cells cultured in vitro. In this work, the in vivo anti-leukemia activity of NPM was investigated using a bioluminescent mouse model. The luciferase–expressing Jurkat cells (Jurkat-Luc) were mixed with matrigel and injected subcutaneously into the nude mice. Drug treatment was commenced on day 7 after tumor implantation. The growth of xenografted tumors was significantly inhibited in the mice treated with NPM, which is comparable to the inhibitory effect of a classical anti-leukemia drug, cyclophosphamide. Combined treatment with NPM and cyclophosphamide further enhanced the growth inhibition of xenografted Jurkat-Luc cells. Immunohistochemistry staining with cleaved caspase 3 (cl-caspase 3) indicated a very heavy staining of cl-caspase 3 only in the tumor implants excised from the NPM-treated mice. We conclude that NPM induced apoptosis and inhibited the growth of xenografted Jurkat-Luc cells in nude mice, demonstrating that NPM displays anti-leukemia activity in vivo.
Original language | English |
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Pages (from-to) | 64-69 |
Number of pages | 6 |
Journal | Leukemia Research |
Volume | 62 |
DOIs | |
State | Published - 11 2017 |
Bibliographical note
Publisher Copyright:© 2017 Elsevier Ltd
Keywords
- Anticancer drug
- Bioluminescent mouse model
- N-(1-Pyrenyl) maleimide
- T-cell acute lymphoblastic leukemia
- Telomerase inhibitor