Cessation of cell proliferation by adjustment of cell redox potential

A variety of chemical substances are known to stop cell proliferation, although the mechanisms are obscure. We suggest that many of these chemicals employ the braking power of the retinoblastoma {RB) protein to stop proliferation by raising the intracellular redox potential. The elevation of the redox potential above a threshold prevents the phosphorylation of RB protein, which in turn impedes the release of transcription factors necessary for the progression of the cell cycle. The redox potential of normal proliferating fibroblasts has been found to be below that of fibrosarcoma cells. The possibility thus exists that, for cells with this property, the dosage of a redox-raising agent can be adjusted to stop cancer-cell proliferation without affecting the proliferation of normal cells. (C) 2001 Academic Press.