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 G2 into mitosis is mainly controlled by formation of the cyclin B1/p34cdc2 complex. The behaviour of this complex in the irradiation-induced G2 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 G2 block abrogator. The present study shows that irradiation, and 2 mM pentoxifylline affect the expression of the cyclin-dependent kinase p34cdc2 in HeLa cells. Irradiation induces p34cdc2 levels to increase and cyclin B1 levels to decrease. Addition of pentoxifylline at the G2 maximum reverses these trends. This is also evident from the cyclin B1/p34cdc2 ratios which decline after irradiation and are rapidly restored to control levels upon addition of pentoxifylline. It is concluded that cyclin BI and p34cdc2 protein expression are important events and act in concert to control the irradiation induced G2 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 G2 block is abrogated by pentoxifylline.
Theron
T
T
Department of Radiation Oncology, University of Stellenbosch Medical Faculty, Tygerberg, South Africa.
Böhm
L
L
D016203:CDC2 Protein Kinase / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism / Q000528:radiation effects; D019926:Cyclin B / Q000378:metabolism*; D056744:Cyclin B1; D003593:Cytoplasm / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D005434:Flow Cytometry; D016195:G2 Phase / Q000187:drug effects* / Q000528:radiation effects; D006367:HeLa Cells; D006801:Humans; D010431:Pentoxifylline / Q000494:pharmacology*
C534699:CCNB1 protein, human; D019926:Cyclin B; D056744:Cyclin B1; D004247:DNA; D016203:CDC2 Protein Kinase; D010431:Pentoxifylline