The effect of melatonin on cell cycle progression
was dependent on the metabolic and differentiation status
of the cells. In this regard, 1 mM melatonin 72 hours
treatment induced an arrest at G2/M and G1/G0 phases
respectively for the resistant Glu-CSCs and Glu-dCCs
groups (p < 0.05). On the other hand, 1 mM melatonin
induced an arrest at S-phase in both P19 cell groups
cultured in galactose (glucose-free), glutamine/pyruvatecontaining
medium (p < 0.001) at expenses of reducing the
number of cells on G2/M phase for Gal-CSCs, and on G1/
G0 phase for Gal-dCCs (Figure 1C).
Melatonin modulates calcium homeostasis [25], a
critical step to maintain a regular cell cycle progression.
The four groups of P19 cells showed different basal
levels of intracellular free calcium, being the highest
concentration observed in P19 cells grown in galactose
(glucose-free), glutamine/pyruvate- containing medium.
In these groups of P19 cells cultured in the modified
galactose media, 1 mM melatonin along 72 hours
treatment resulted in decreased amount of free calcium
(p < 0.05) in clear contrast to the results in the resistant
Glu-CSCs (Figure 1D).