Influence of the G2 cell cycle block abrogator pentoxifylline on the expression and subcellular location of cyclin B1 and p34cdc2 in HeLa cervical carcinoma cells

The progression of cells from G(2) into mitosis is mainly controlled by formation of the cyclin B1/p34(cdc2) complex. The behaviour of this complex in the irradiation-induced G(2) cell cycle delay is still unclear. A prior study demonstrated that the expression of the cyclin B1 protein is reduced by irradiation, and restored to control levels by the methylxanthine drug pentoxifylline, which is a potent G(2) block abrogator. The present study shows that irradiation, and 2 mM pentoxifylline affect the expression of the cyclin-dependent kinase p34(cdc2) in HeLa cells. Irradiation induces p34(cdc2) levels to increase and cyclin B1 levels to decrease. Addition of pentoxifylline at the G(2) maximum reverses these trends. This is also evident from the cyclin B1/p34(cdc2) ratios which decline after irradiation and are rapidly restored to control levels upon addition of pentoxifylline. It is concluded that cyclin B1 and p34(cdc2) protein expression are important events and act in concert to control the irradiation induced G(2) block. Analysis of cyclin B1 expression in whole cells and in isolated nuclei furthermore show that cyclin B1 is translocated from the nucleus into the cytoplasm when the G(2) block is abrogated by pentoxifylline.