Abstract
It has been recently shown that the type I insulin-like growth factor receptor (IGF-IR) contributes significantly to the survival of T lymphoblastic leukemia/lymphoma (T-LBL) cells, and it was therefore suggested that IGF-IR could represent a legitimate therapeutic target in this aggressive disease. Picropodophyllin (PPP) is a potent, selective inhibitor of IGF-IR that is currently used with notable success in clinical trials that include patients with aggressive types of epithelial tumors. In the present study, we tested the effects of PPP on Jurkat and Molt-3 cells; two prototype T-LBL cell lines. Our results demonstrate that PPP efficiently induced apoptotic cell death and cell cycle arrest of these two cells. These effects were attributable to alterations of downstream target proteins. By using proteomic analysis, seven different proteins were found to be affected by PPP treatment of Jurkat cells. These proteins are involved in various aspects of cellular metabolism, cytoskeleton organization and signal transduction pathways. The results suggest that PPP affects multiple signaling molecules and inhibits fundamental pathways that control cell growth and survival. Our study also provides novel evidence that PPP could be potentially utilized for the treatment of aggressive T-LBL.
Potential conflict of interest:
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This work was sponsored by grants from the National Natural Science Foundation of China (31100549), Shanghai Pujiang Programs (10PJ1402300 and 11PJ1400100), Innovation Program of Shanghai Municipal Education Commission (11ZZ51), the Scientific Research Foundation for Returned Overseas Chinese Scholars, State Education Ministry and Fundamental Research Funds for the Central Universities (WF1114020 and 222201313010). H.M.A. is supported by R01 CA151533 grant from the National Cancer Institute. The contents of this paper are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.