What is the effect of SGI-1776 on Mcl-1 and cyclin D1 protein levels in MCL cells?

Mcl-1 and cyclin D1 are short-lived proteins that play critical roles in cell survival and proliferation in MCL. Pim kinases, which are inhibited by SGI-1776, are involved in stabilizing these proteins through transcriptional and translational regulation.

SGI-1776 treatment leads to a dose- and time-dependent decrease in Mcl-1 and cyclin D1 protein levels in MCL cell lines such as JeKo-1 and Mino. In JeKo-1 cells, Mcl-1 protein levels decrease significantly at 3 µM and higher concentrations, while in Mino cells, a more pronounced decrease is observed at 10 µM. Cyclin D1 levels also decline in JeKo-1 cells but increase in Mino cells, possibly due to cell cycle changes. This suggests that SGI-1776-induced degradation of these proteins contributes to cell death in MCL cells.