Addiction to c-MYC in 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.
KG Jebsen Center for Myeloma Research and Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway. toril.holien@ntnu.no
Toril
T
Holien
Thea Kristin
TK
Våtsveen
Hanne
H
Hella
Anders
A
Waage
Anders
A
Sundan
D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000187:drug effects; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013844:Thiazoles / Q000494:pharmacology
C524814:5-(4-ethylbenzylidene)-2-thioxothiazolidin-4-one; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D013844:Thiazoles