Cell membrane changes of structure and function in protein kinase inhibitor-induced polyploid cells.

Exogenous cyclic AMP has been thought to be a chemical without marked pharmacological effect until now, as it is not capable of penetrating the cell membrane in most eucaryotic cells. The present study obtained results consistent 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 microM. However, it was found that K252a, a potent inhibitor of protein kinases including protein kinase C, induced DNA re-replication, i.e. DNA synthesis at a elevated DNA ploidy in cells that had not undergone cytokinesis (leading to polyploidization), and that exogenous cyclic AMP markedly potentiated the K252a-induced polyploidization at a very low dose similar to the effective dose of membrane-permeable cyclic AMP analogue dibutyryl cyclic AMP. These findings suggested that the cell membrane changed during the formation 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.

[Induction of phenotypic reverse transformation by plant glycosides in cultured cancer cells].

Crude ginsenosides extracted from the root of Panax ginseng C.A. Meyer inhibited the growth and colony forming ability of Morris hepatoma cells in soft agar suspension culture, and stimulate the serum protein synthesis of these cells, thus converting the cell characteristics both functionally and morphologically to those resembling original normal liver cells. We have called such a phenomenon "reverse transformation" or "redifferentiation" which can be regarded as decarcinogenesis. In this report, the results of our recent investigations are presented with particular reference to reverse transformation of B16 melanoma cells induced by ginsenoside Rh2 isolated from the methanol extract of crude ginseng saponin fraction and action mechanisms of ginsenoside Rh2 are also discussed.