CDDO-Imidazolide inhibits growth and survival of c-Myc-induced mouse B cell and plasma cell neoplasms

Background: Gene-targeted iMyc^Eμ mice that carry a His₆-tagged mouse Myc(c-myc)cDNA, Myc^His, just 5′ of the immunoglobulin heavy-chain enhancer, Eμ, are prone to B cell and plasma cell neoplasms, such as lymphoblastic B-cell lymphoma (LBL) and plasmacytoma (PCT). Cell lines derived from Myc-induced neoplasms of this sort may provide a good model system for the design and testing of new approaches to prevent and treat MYC-driven B cell and plasma cell neoplasms in human beings. To test this hypothesis, we used the LBL-derived cell line, iMyc^Eμ-1, and the newly established PCT-derived cell line, iMyc^Eμ-2, to evaluate the growth inhibitory and death inducing potency of the cancer drug candidate, CDDO-imidazolide (CDDO-Im). Methods: Morphological features and surface marker expression of iMyc^Eμ-2 cells were evaluated using cytological methods and FACS, respectively. mRNA expression levels of the inserted Myc_His and normal Myc genes were determined by allele-specific RT-PCR and qPCR. Myc protein was detected by immunoblotting. Cell cycle progression and apoptosis were analyzed by FACS. The expression of 384 "pathway" genes was assessed with the help of Superarray