Gonadotropin-releasing hormone analogues inhibit cell proliferation and activate signal transduction pathways in MDA-MB-231 human breast cancer cell line

A novel gonadotropin-releasing hormone (GnRH) agonist (folligen) which stimulates follicular maturation has been developed in our laboratory. The direct effect of folligen and a well-known superactive GnRH analogue, buserelin, on the MDA-MB-231 human breast cancer cell line was investigated. Folligen was found to be slightly more active in inhibiting cell proliferation than buserelin, and significant differences were found in the signal transduction pathways activated by these analogues. These results demonstrate for the first time that tyrosine kinases and/or phospholipid turnover together with protein kinase C activation can be directly involved in the antitumor activity of GnRH analogues. The results also suggest that folligen and buserelin might have a different mechanism of action on this human breast cancer cell line.