Melatonin and RZR/ROR receptor ligand CGP 52608 induce apoptosis in the murine colonic cancer.

The effects of melatonin and the thiazolinidinedione derivative CGP 52608 on apoptosis of Colon 38 cancer cells were investigated. Male mice were implanted subcutaneously with a suspension of Colon 38 cells. Ten days after induction of tumors, the animals were treated with melatonin or CGP 52608. Both substances were given in subcutaneous injections in daily doses of 10 or 100 microg in the evening for 6 days. The control group received solvent. The apoptotic cells were visualized in paraffin sections by means of the transferase-mediated dUTPnick end-labeling method. Both treatments increased significantly and to the same degree the number of apoptotic cells in tumors. This finding confirms our earlier observation that melatonin exerts a pro-apoptotic effect on murine colonic cancer cells. Moreover, because CGP 52608 is a ligand of RZR/ROR receptors and the latter are considered by some investigators as nuclear binding sites for melatonin, our data suggest the involvement of these receptors in the pro-apoptotic effect of melatonin.