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 apoptosis induced by low doses of 6-hydroxydopamine (6-OHDA) in undifferentiated and neuronal PC12 cells. We also reported how this neurohormone was able to prevent the decrease in the mRNA for antioxidant enzymes caused by 6-OHDA. Although the antioxidant capability of melatonin seems to be clearly implicated in its antiapoptotic activity, literature suggests that its antiproliferative property could also be involved in its prevention of apoptosis. In the present work we demonstrated that melatonin is able to inhibit cell proliferation in undifferentiated 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 synthesis. Melatonin does not decrease the number of cells in nonproliferating PC12 cells, indicating that it does not cause cell death. Additionally, we demonstrate that other inhibitors of cell proliferation, as well as other antioxidants, are able to mimic the antiapoptotic effect of melatonin. This is interpreted to mean that melatonin acts by both mechanisms to inhibit apoptosis caused by 6-OHDA and the findings support the hypothesis of a relationship between oxidative stress and regulation of the cell cycle.
Departamento de Morfología y Biología Celular, Universidad de Oviedo, Facultad de Medicina, Spain.
J C
JC
Mayo
R M
RM
Sainz
H
H
Uría
I
I
Antolín
M M
MM
Estéban
Rodríguez
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D015152:Blotting, Northern; D002452:Cell Count; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D004247:DNA / Q000378:metabolism; D053938:DNA Fragmentation; D006657:Histones / Q000235:genetics / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D016627:Oxidopamine / Q000494:pharmacology; D016716:PC12 Cells / Q000166:cytology* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats
D000970:Antineoplastic Agents; D000975:Antioxidants; D006657:Histones; D012333:RNA, Messenger; D016627:Oxidopamine; D004247:DNA; D008550:Melatonin