Gonadotropin releasing hormone is the hypothalamic hormone that activates pituitary gonadotropin production and, ultimately, determines reproductive competence[3]. The gonadotropin-releasing hormone receptor (GnRHR) is a guanine nucleotide-binding protein-coupled receptor with a characteristic seven transmembrane domain motif. It transduces the hypothalamic message carried by the decapeptide gonadotropin-releasing hormone. At the gonadotrope cell surface the hormone binds to the receptor, leading to pituitary synthesis and secretion of gonadotropins. These glycoprotein hormones, in turn, modulate folliculogenesis and ovulation in the ovary[4].Cetrorelix Acetate (SB-75 acetate) is a potent gonadotropin-releasing hormone (GnRH) receptor antagonist with an IC50 of 1.21 nM [5].Treatment with Cetrorelix inhibited growth and colony-forming ability of myeloma cells, including cell lines resistant to arsenic trioxide, bortezomib, or lenalidomide. Cetrorelix induced apoptosis in myeloma cells including primary myeloma cells. In addition, Cetrorelix inhibited the growth of human myeloma cells xenografted into mice without any apparent side effects. Cetrorelix downregulated the nuclear factor-kappa B (NF-κB) pathway activity and the expression of cytokines, including interleukin 6, insulin-like growth factor 1, VEGF-A, and stromal-derived factor 1, important for myeloma cell growth and survival in myeloma cells and/or marrow stromal cells from myeloma patients. Cetrorelix decreased the phosphorylation of extracellular signal regulated kinase 1/2 and STAT3 in myeloma cells, two crucial pathways for myeloma cells growth and survival. Moreover, the expression of p21 and p53 was increased, whereas that of antiapoptotic proteins Bcl-2 and Bcl-x(L) was reduced by Cetrorelix[6].
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