Effects of melatonin and melatonin receptors ligand N-[(4-methoxy-1H-indol-2-yl)methyl]propanamide on murine Colon 38 cancer growth in vitro and in vivo.
OBJECTIVE
Our previous study suggest that oncostatic action of melatonin (MLT) depends mainly on nuclear RZR/ROR receptors. However, we cannot exclude the involvement of membrane receptors in the control of tumor growth. In the present study the effects of MLT and N-[(4-methoxy-1H-indol-2-yl)methyl]propanamide (UCM 386 - antagonist of membrane MT(1) receptor and partial agonist of membrane MT(2) receptor) on murine transplantable Colon 38 cancer were investigated in vitro and in vivo conditions.


METHODS
The experiments were performed on adult male B6D2F1 mice strain. In vitro the cell proliferation was measured using modified Mosmann method. In the experiment performed in vivo, we assessed the cell proliferation, apoptosis and proliferation/apoptosis ratio (P/A). The incorporation of bromodeoxyuridine into tumor cell nuclei was used as an index of cell proliferation (labeling index-LI). The labeling of apoptotic cells according to TUNEL method was considered as an index of apoptosis (AI).


RESULTS
In vitro MLT and UCM 386 decreased the cell proliferation, but administration of MLT and UCM 386 together did not change the inhibitory effect of MLT alone. In vivo MLT and UCM 386 alone decreased LI and the addition of UCM 386 to MLT did not diminish the antiproliferative effect of MLT. Melatonin and UCM 386 injected alone also increased the AI. Moreover, both compounds given together exerted the additive effect on tumor apoptosis. MLT and UCM 386 alone or together also significantly decreased P/A ratio which is additional parameter confirming the inhibition of tumor growth.


CONCLUSIONS
The obtained data together with our earlier observations suggest that oncostatic effect of MLT depends on acting via both MT(2) and RZR/ROR nuclear receptors
Winczyk
Katarzyna
K
Department of Experimental Endocrinology and Hormone Diagnostics, Institute of Endocrinology, Medical University of Lodz, Lodz, Poland.
Pawlikowski
Marek
M
Lawnicka
Hanna
H
Kunert-Radek
Jolanta
J
Spadoni
Gilberto
G
Tarzia
Giorgio
G
Karasek
Michal
M
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001973:Bromodeoxyuridine; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D007211:Indoles / Q000494:pharmacology*; D008024:Ligands; D008550:Melatonin / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation; D011956:Receptors, Cell Surface / Q000819:agonists*; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists*; D044094:Receptors, Melatonin; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D000975:Antioxidants; D007211:Indoles; D008024:Ligands; C435190:N-((1-(4-chlorobenzyl)-4-methoxy-1H-indol-2-yl)methyl)propanamide; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D044094:Receptors, Melatonin; D001973:Bromodeoxyuridine; D008550:Melatonin