Inhibition of protein kinase B activity induces cell cycle arrest and apoptosis during early G₁ phase in CHO cells

Abstract

Inhibition of PKB (protein kinase B) activity using a highly selective PKB inhibitor resulted in inhibition of cell cycle progression only if cells were in early G1 phase at the time of addition of the inhibitor, as demonstrated by time-lapse cinematography. Addition of the inhibitor during mitosis up to 2 h after mitosis resulted in arrest of the cells in early G1 phase, as deduced from the expression of cyclins D and A and incorporation of thymidine. After 24 h of cell cycle arrest, cells expressed the cleaved caspase-3, a central mediator of apoptosis. These results demonstrate that PKB activity in early G1 phase is required to prevent the induction of apoptosis. Using antibodies, it was demonstrated that active PKB translocates to the nucleus during early G1 phase, while an even distribution of PKB was observed through cytoplasm and nucleus during the end of G1 phase.

Carcinoma-associated fibroblasts affect sensitivity to oxaliplatin and 5FU in colorectal cancer cells

“…Once activated, different AKT isoforms translocate to diverse subcellular compartments to exert specific functions depending on the location [ 27 ]. Nuclear translocation of AKT during G1 in particular has been associated with cell cycle progression [ 33 ], Cyclin D1 expression [ 34 ] and DNA repair after double-strand breaks (DSBs) [ 35 ]. Additionally, different growth factors and soluble molecules have been reported to induce nuclear translocation of AKT (e.g., IGF1, insulin and NGF) [ 36 , 37 , 38 ].…”