title: Inhibition of type I insulin-like growth factor receptor tyrosine kinase by picropodophyllin induces apoptosis and cell cycle arrest in T lymphoblastic leukemia/lymphoma.
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.
authors.affiliation: College of Chemistry, Chemical Engineering and Biotechnology, Donghua University , Shanghai , China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Huang
authors.forename: Zhijia
authors.initials: Z
authors.lastname: Fang
authors.forename: Hong
authors.initials: H
authors.lastname: Zhen
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.forename: Hesham M
authors.initials: HM
authors.lastname: Amin
authors.forename: Ping
authors.initials: P
authors.lastname: Shi
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D019169:Jurkat Cells; D010766:Phosphorylation / Q000187:drug effects; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000494:pharmacology; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D040901:Proteomics; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C415032:picropodophyllin; D011505:Protein-Tyrosine Kinases; D017526:Receptor, IGF Type 1; D011034:Podophyllotoxin
keywords: IGF-IR; Jurkat cells; Molt-3 cells; T lymphoblastic leukemia/lymphoma; picropodophyllin; proteomics