Attenuation of EIF4E Translation Initiation Adversely Affects Multiple Myeloma Cells

This work explores the therapeutic potential for the translation initiation factor eIF4E in multiple myeloma (MM). We show that targeting eIF4E is deleterious to MM cells and causes reduction of targets with established importance to the disease progression. We demonstrate that eIF4E inhibition may be achieved by treating the MM cells with the already clinically employed anti-viral drug Ribavirin. Results indicate that tetraspanin overexpression in MM cell lines increased global protein synthesis; CD81N1/CD82N1 also caused a decrease in peIF4E, its regulators and targets; direct inhibition of eIF4E (siRNA, Ribavirin) deleteriously affected MM cell lines; and Ribavirin attenuated viability and induced death of primary BM MM cells. Multiple Myeloma cell lines RPMI 8226 and CAG were each transiently transfected with purified plasmids of tetraspanins: pEGFP-N1 (N1, control), CD81N1-eGFP (81N1) or CD82N1-eGFP (82N1) (Clontech). Transfected cells were separated by Sorter Flow Cytometer 24 hours after transfection. Total RNA was extracted from sorted transfected cells with the Qiagen kit. Three separate experiments were analyzed by Whole Genome Affymetrix microarray chips (N1, 81N1, 82N1 in each cell line).