publication . Other literature type . Article . 2011

Resistance to the Translation Initiation Inhibitor Silvestrol is Mediated by ABCB1/P-Glycoprotein Overexpression in Acute Lymphoblastic Leukemia Cells

Gupta, Sneha V.; Sass, Ellen J.; Davis, Melanie E.; Edwards, Ryan B.; Lozanski, Gerard; Heerema, Nyla A.; Lehman, Amy; Zhang, Xiaoli; Jarjoura, David; Byrd, John C.; ...
  • Published: 04 May 2011
  • Publisher: Springer Science and Business Media LLC
Abstract
Protein synthesis is a powerful therapeutic target in leukemias and other cancers, but few pharmacologically viable agents are available that affect this process directly. The plant-derived agent silvestrol specifically inhibits translation initiation by interfering with eIF4A/mRNA assembly with eIF4F. Silvestrol has potent in vitro and in vivo activity in multiple cancer models including acute lymphoblastic leukemia (ALL) and is under pre-clinical development by the US National Cancer Institute, but no information is available about potential mechanisms of resistance. In a separate report, we showed that intraperitoneal silvestrol is approximately 100% bioavail...
Subjects
free text keywords: Chemistry, Romidepsin, medicine.drug, medicine, Pharmacology, Leukemia, medicine.disease, P-glycoprotein, biology.protein, biology, Downregulation and upregulation, Efflux, Rhodamine 123, chemistry.chemical_compound, Vincristine, Cell culture, Research Paper
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