Oridonin Induces Apoptosis of Myeloma Cells by Inducing C-Myc Degradation via Nuclear Accumulation of Fbxw7α

The overall survival of patients with multiple myeloma has recently improved, primarily due to the use of several novel agents, including proteasome inhibitors and immunomodulatory drugs. However, as MM remains incurable due to its eventual relapse, the development of more effective agents is greatly needed. Oridonin is a diterpenoid that induces apoptosis and autophagy in various types of cancer. However, the effects of oridonin on MM cells have not been fully elucidated. In the present study, we found that oridonin inhibited proliferation and induced caspase-dependent apoptosis in MM cells. Interestingly, oridonin suppressed c-Myc protein levels and promoted the nuclear accumulation of F-box and WD-40 domain protein 7α, a component of the SCF-like ubiquitin ligase complex, suggesting that oridonin induced c-Myc down regulation might at least in part be due to proteasomal degradation of c-Myc via Fbxw7α-mediated ubiquitination. These results suggest that the effects of oridonin in MM patients in the clinical setting warrant investigation.