Effects of Melatonin and CGP 52608 on the Murine Colon 38 Adenocarcinoma.
In Vitro and In Vivo by Michal
Karasek, Katarzyna Winczyk, Jolanta Kunert-Radek, Irmgard Wiesenberg
& Marek Pawlikowski
pineal gland hormone melatonin and structurally novel class
of thiazolidinediones represented by the lead structure CGP
52608 have been shown to specifically activate the receptor
RZR/RORa, a member of the nuclear
receptor superfamily of ligand-inducible transcription factors.
The effects of melatonin and CGP 52608 on the proliferation
of the murine Colon 38 adenocarcinoma cells were studied in
vitro and in vivo. Melatonin and CGP 52608, inhibited in vitro
[3H]-thymidine incorporation into DNA
in concentrations of 10-5, 10-7
and 10-9 M, with the most effective being
10-7 M. Tumor cell proliferation in vivo
as measured by bromodeoxyuridine incorporation was also significantly
inhibited by daily subcutaneous injections of melatonin or CGP
52608 (10µg and 100 µg/animal). These results do not finally
prove, but support the hypothesis that nuclear signaling via
RZR/RORa receptors may be involved,
at least in part, in mediating the oncostatic effects of the
pineal gland hormone melatonin.