INHIBITION OF CELL-PROLIFERATION - A MECHANISM LIKELY TO MEDIATE THE PREVENTION OF NEURONAL CELL-DEATH BY MELATONIN

In a previous work we demonstrated that melatonin is able to prevent a poptosis induced by low doses of 6-hydroxydopamine (6-OHDA) in undiffe rentiated and neuronal PC12 cells. We also reported how this neurohorm one was able to prevent the decrease in the mRNA for antioxidant enzym es caused by 6-OHDA. Although the antioxidant capability of melatonin seems to be clearly implicated in its antiapoptotic activity, literatu re suggests that its antiproliferative property could also be involved in its prevention of apoptosis. In the present work we demonstrated t hat melatonin is able to inhibit cell proliferation in undifferentiate d PC12 cells, decreasing cell number and the total amount of DNA, and the mRNA for the histone H4, which are known to increase during DNA sy nthesis. Melatonin does not decrease the number of cells in nonprolife rating PC12 cells, indicating that it does not cause cell death. Addit ionally, we demonstrate that other inhibitors of cell proliferation, a s well as other antioxidants, are able to mimic the antiapoptotic effe ct of melatonin. This is interpreted to mean that melatonin acts by bo th mechanisms to inhibit apoptosis caused by 6-OHDA and the findings s upport the hypothesis of a relationship between oxidative stress and r egulation of the cell cycle.