ABSTRACT
Gonadotropin releasing hormone (GnRH) has a pivotal role in the biology of reproduction processes. In extrapituitary compartments GnRH and its receptor act as a part of the autocrin regulatory system of cell proliferation, resulting in its anticancer activity. Here the anticancer activity of a new analogue of GnRH has been investigated. Results indicate that proliferation of human breast and ovarian cancer cell lines is dose-dependently inhibited. The inhibitory efficiency of this new analogue is proved to be higher than the original triptorelin. In addition to its antimitogenic activity, evidence was found for the involvement of the apoptotic mechanism in the action of the new analogue. Furthermore the presence of chemical groups in the peptide sequence is thought to increase the protease stability of the new analogue in comparison with triptorelin. Consequently our new analogue can be considered as a good pharmaceutical candidate.
Subject(s)
Antineoplastic Agents, Hormonal/pharmacology , Gonadotropin-Releasing Hormone/analogs & derivatives , Gonadotropin-Releasing Hormone/pharmacology , Amino Acid Sequence , Antineoplastic Agents, Hormonal/chemistry , Breast Neoplasms , Cell Line, Tumor/drug effects , Cell Proliferation/drug effects , Female , Gonadotropin-Releasing Hormone/chemistry , Humans , Molecular Structure , Ovarian Neoplasms , Triptorelin Pamoate/pharmacologyABSTRACT
Gonadotropin releasing hormone (GnRH) plays a key role in reproduction. This decapeptide is synthesized and released by hypothalamus and induces the pituitary gonadotrop cells to release pituitary gonadotropin hormones. In some extrapituitary compartments GnRH and its receptor act as part of the autocrine regulatory system of cell proliferation. The anticancer activity of GnRH and its analogues has been observed by many researchers. In this study the anticancer activity of a new analogue of GnRH and triptorelin was investigated by cell proliferation assay. Results indicate that proliferation of human breast and ovarian cancer cell lines are dose-dependently inhibited. The inhibitory efficiency of the new analogue is proved to be higher than the original triptorelin. In addition to its antimitogenic activity, evidence was found for the involvement of the apoptotic mechanism in the action of the new analogue and triptorelin. In conclusion, the new analogue can be considered as a good pharmaceutical candidate.
