5-(4-ethylbenzylidene)-2-thioxothiazolidin-4-one and Multiple-Myeloma

In multiple myeloma, c-MYC is activated and contributes to the malignant phenotype. Targeting MYC by short hairpin RNA induced cell death in myeloma cell lines; however, cell lines are generated from samples taken in advanced stages of the disease and may not reflect patient cells adequately. In this study, we used the selective small molecule inhibitor of MYC-MAX heterodimerization, 10058-F4, on myeloma cell lines as well as primary myeloma cells, and we show that inhibition of c-MYC activity efficiently induces myeloma cell death. Moreover, in cocultures of cell lines with bone marrow stromal cells from myeloma patients, the inhibitor still induces apoptosis. Our results provide further evidence that myeloma cells are addicted to c-MYC activity and that c-MYC is a promising therapeutic target in multiple myeloma.

Topics: Apoptosis; Cell Line, Tumor; Cell Proliferation; Gene Expression Regulation, Neoplastic; Humans; Mesenchymal Stem Cells; Multiple Myeloma; Proto-Oncogene Proteins c-myc; Thiazoles

Topics: Apoptosis; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Bone Morphogenetic Proteins; Cell Line, Tumor; Down-Regulation; Genes, myc; Humans; Multiple Myeloma; Proto-Oncogene Proteins c-myc; Repressor Proteins; RNA Interference; Signal Transduction; Thiazoles