Cessation of cell proliferation by adjustment of cell redox potential

A variety of chemical substances are known to stop cell proliferation, alth ough the mechanisms are obscure. We suggest that many of these chemicals em ploy the braking power of the retinoblastoma {RB) protein to stop prolifera tion by raising the intracellular redox potential. The elevation of the red ox potential above a threshold prevents the phosphorylation of RB protein, which in turn impedes the release of transcription factors necessary for th e progression of the cell cycle. The redox potential of normal proliferatin g fibroblasts has been found to be below that of fibrosarcoma cells. The po ssibility thus exists that, for cells with this property, the dosage of a r edox-raising agent can be adjusted to stop cancer-cell proliferation withou t affecting the proliferation of normal cells. (C) 2001 Academic Press.