We tested the effects of daily melatonin treatment on the growth of th
e ascites hepatoma in rats, determining survival time, cell number and
cell cycle phases at various stages of tumor development. Melatonin i
nhibited cellular proliferation, doubled mean life-time and increased
survival. Thymidine incorporation in hepatoma cells from treated rats
decreased significantly without changes in the apoptotic index. Flow c
ytometric analysis showed that melatonin slowed cell cycle progression
by increasing the number of cells in phase G0G1. Thus, similar to in
vitro models, melatonin's oncostatic action in vivo appears to be dire
cted to specific cell cycle mechanisms, which remain to be elucidated.
(C) 1998 Elsevier Science Ireland Ltd.