Direct anticancer activity of gonadotropin-releasing hormone-III.
In previous studies GnRH-III, a variant of the hypothalamic neurohormone GnRH, was isolated from the brain of the sea lamprey and structurally characterized. GnRH-III is a hypothalamic neurohormone in both female and male sea lampreys. In the present work biological activities of GnRH-III in mammalian systems were examined. In superfused rat pituitary cells, GnRH-III at 1 nM to 100 nM neither induced LH-secretion nor inhibited the LH-secretion elicited by native GnRH and elicited LH release only at 1 microM. At high dose (500 microg/day) in vivo, GnRH-III behaved as a GnRH agonist, though, it was 1000-fold less active than ovurelin. The in vitro and in vivo results were in good agreement in showing that GnRH-III is only a weak agonist of the endocrine activity of GnRH. GnRH-III specifically bound to receptors on cancer cells and recognized not only the high-, but also the low-affinity binding sites. GnRH-III significantly suppressed growth of human cancer cells which have GnRH receptors. The inhibitory effect of GnRH-III on growth of cancer cells was specific and direct since the peptide did not have endocrine activity in the concentration range found to be effective in anticancer assays. GnRH-III inhibited equally the growth of ER-positive and -negative breast and TeR-positive and negative prostate cells.
Lovas
S
S
Department of Biomedical Sciences, Creighton University, Omaha, Nebraska 68178, USA. vasz@bifi.creighton.edu
Pályi
I
I
Vincze
B
B
Horváth
J
J
Kovács
M
M
Mezö
I
I
Tóth
G
G
Teplán
I
I
Murphy
R F
RF
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011966:Receptors, LHRH / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone