Concomitant differentiation and partial proteasome inhibition trigger apoptosis in neuroblastoma cells.

摘要: Proteasome activity is essential during cAMP-induced terminal differentiation of a murine neuroblastoma cell line (NBP2). However, the mechanisms through which proteasome affects NBP2 have not been characterized. We hypothesized that required to implement differentiation-mediated effects on cycle, and its partial inhibition may adverse consequences. Here we show cells causes apoptosis. Whereas induced growth arrest at G1 phase, resulted in accumulation G2M phase. Cell cycle data correlated with level cyclin-dependent kinase inhibitors p21WAF p27Kip1, cyclin A. While p21 p27 increased, A decreased upon differentiation. In contrast, treated inhibitor presence cAMP-inducing agents showed increased levels early course p27, but A, later concomitant when were undergoing Our suggest dependent temporal proteins. Partial interferes events partly by stabilizing proteins this triggers Thus, differentiating drugs combined impart higher therapeutic efficacy than alone for treatment tumors.