Preferential killing of melanoma cells by a p16-related peptide

Abstract

We report the identification of a synthetic, cell-penetrating peptide able to kill human melanoma cells efficiently and selectively, while less toxic to normal human melanocytes and nontoxic to human fibroblasts. The peptide is based on the target-binding site of the melanoma suppressor and senescence effector p16 (INK4A, CDKN2A), coupled to a cell-penetrating moiety. The killing is by apoptosis and appears to act by a route other than the canonical downstream target of p16 and CDK4, the retinoblastoma (RB) family, since it is also effective in HeLa cells and a melanocyte line expressing HPV E7 oncogenes, which both lack any active RB. There was varying toxicity to other types of cancer cell lines such as glioblastoma. Melanoma cell killing by a p16-derived peptide was reported once before but only at a higher concentration, while selectivity and generality were not previously tested.

P16-CD8-Ki67 Triple Algorithm for Prediction of CDKN2A Mutations in Patients with Multiple Primary and Familial Melanoma

“…The research by Soo et al published in 2023 reported the identification of a synthetic peptide capable of cell penetration and induction of apoptosis of neoplastic melanoma cells in an efficient and selective manner, with the advantage of lower toxicity to normal melanocytes and absence of human fibroblasts [38]. This peptide is based on the targetbinding site of the p16 effector involved in senescence and suppression of melanoma progression, combined with a fraction that facilitates intracellular penetration [39].…”