Zp. Zong et al., Cell membrane changes of structure and function in protein kinase inhibitor-induced polyploid cells, CELL PROLIF, 33(1), 2000, pp. 29-38
Exogenous cyclic AMP has been thought to be a chemical without marked pharm
acological effect until now, as it is not capable of penetrating the cell m
embrane in most eucaryotic cells. The present study obtained results consis
tent with those of most previous studies, showing that exogenous cyclic AMP
itself did not interfere with the cell cycle even at the high dose of 100
mu M. However, it was found that K252a, a potent inhibitor of protein kinas
es including protein kinase C, induced DNA re-replication, i.e. DNA synthes
is at a elevated DNA ploidy in cells that had not undergone cytokinesis (le
ading to polyploidization), and that exogenous cyclic AMP markedly potentia
ted the K252a-induced polyploidization at a very low dose similar to the ef
fective dose of membrane-permeable cyclic AMP analogue dibutyryl cyclic AMP
. These findings suggested that the cell membrane changed during the format
ion of polyploid cells. This supposition was confirmed by scanning electron
microscopy to observe structural changes and by determination of cellular
attachment to investigate functional changes.