Cell cycle arrest mediated by a pyridopyrimidine is not abrogated by over-expression of Bcl-2 and cyclin D1

Inhibition of cyclin dependent kinases (Cdks) is of pivotal importance in t umor cell biology as these kinases are the drivers of cell proliferation. T his inhibition can be achieved either by naturally occurring biological pro teins or by small molecule compounds. They cause cell cycle arrest and/or a poptosis depending upon the specificity and efficacy of the inhibitor in qu estion. We have reported earlier that specific pyridopyrimidines (novel Cdk inhibitors) cause cell cycle arrest in mink lung epithelial cells and the arrest is abrogated by over-expression of Cdk4. In contrast, we show here t hat one of these inhibitors effectively maintains cell cycle arrest in a le ukemic or a breast cancer cell line even after the respective cells over-ex press an oncogene, either Bcl-2 or cyclin D1. However, in the leukemic cell s, Bcl-2 over-expression suppresses apoptosis induced by the pyridopyrimidi ne. Thus, novel Cdk inhibitors can prove to be useful chemical genetics too ls for understanding the underlying mechanisms of growth arrest and/or apop tosis in normal versus tumor cells. This could also lead to the development of improved inhibitors of cell proliferation.