Novel Synthetic Kisspeptin Derivatives Impair Wound Healing in Breast Adenocarcinoma

Abstract

Currently, cancer plays an important role in public health. Mortality from cancer in 90% of cases is caused by the development of metastases, which are the clinical result of the invasiveness of the pathology. Among the known metastasis suppressor molecules are the products of the KISS1 gene—the metastin protein and its derivatives: kisspeptin-14 (KP14), kisspeptin-13 (KP13) and kisspeptin-10 (KP10). The KISS1/KISS1R system regulates the development and progression of several types of cancer. These molecules are important in the development of new treatment methods and/or as markers in the treatment of cancer, so the biologically active kisspeptin analogues design and synthesis is a promising direction for the development of drugs that prevent the metastases formation. In this study, promising sequences of kisspeptin and its modified analogues—KP-10, KP-10-dAla, KP-6-dAla—were designed. Peptides with a purity of >98% were obtained through chemical synthesis and chromatographic purification. Study of its biological activity on the MCF-7 cell line (breast adenocarcinoma) demonstrated the anti-migration activity of the peptides. The greatest effect was observed with the treatment of 1000 nM KP-10, 10 nM KP-6-dAla, 10 nM KP-10-dAla. It was shown that replacing glycine with D-alanine and shortening the kisspeptin chain led to a slower rate of wound healing of MCF-7 cells compared to control. The potential effectiveness of KP-6-dAla and KP-10-dAla in suppressing metastasis was revealed, thereby making it a promising candidate for the development of anticancer drugs.