Growth-inhibitory action of melatonin and thiazolidinedione derivative CGP 52608 on murine 16/C breast cancer cells.
OBJECTIVE
Melatonin may influence directly tumor cells through the specific binding sites. The best known melatonin binding sites are membrane receptors. Recently, the participation of nuclear signalling via estrogen as well as RZR/ROR receptors in oncostatic action of melatonin on the breast cancer has been widely discussed. The aim of present study was to investigate effects of melatonin, the selective ligand for nuclear RZR/ROR receptors - CGP 52608, and methotrexate on growth of murine 16/C breast cancer cells.


METHODS
The experiment was performed in vitro. The breast cancer cells were incubated for 2 days in the presence of melatonin, CGP 52608 (at concentrations of 10(-5)M, 10(-7)M, 10(-9)M, 10-(11)M ) and methotrexate (at concentrations of 0.25 and 0.125 microg/ml). The growth of cells was measured using the modified Mossman method.


RESULTS
All examined compounds significantly inhibited the growth of cancer cells. The effects of MLT and CGP 52 608 were comparable with suppression caused by methotrexate. The significant differences of efficacy between two examined concentrations of methotrexate were not observed.


CONCLUSIONS
The obtained data together with our previous results indicate that nuclear receptors RZR/ROR play an important, although not sufficiently recognized role in the oncostatic action of melatonin.
Winczyk
Katarzyna
K
Department of Neuroendocrinology, Chair of Endocrinology, Medical University of Lodz, Poland.
Lawnicka
Hanna
H
Pawlikowski
Marek
M
Kunert-Radek
Jolanta
J
Karasek
Michal
M
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008550:Melatonin / Q000008:administration & dosage / Q000378:metabolism*; D008727:Methotrexate / Q000494:pharmacology; D051379:Mice; D057095:Nuclear Receptor Subfamily 1, Group F, Member 2; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid / Q000187:drug effects / Q000378:metabolism*; D018709:Statistics, Nonparametric; D013844:Thiazoles / Q000494:pharmacology; D013882:Thiosemicarbazones / Q000494:pharmacology
D000964:Antimetabolites, Antineoplastic; D018931:Antineoplastic Agents, Hormonal; D057095:Nuclear Receptor Subfamily 1, Group F, Member 2; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D013844:Thiazoles; D013882:Thiosemicarbazones; C092451:CGP 52608; D008550:Melatonin; D008727:Methotrexate