Molecular & Clinical Sciences Research Institute, St George's, University of London, Cranmer Terrace, London SW17 0RE, UK.
Biol Open. 2023 Aug 15;12(8). doi: 10.1242/bio.059965. Epub 2023 Aug 17.
We report the identification of a synthetic, cell-penetrating peptide able to kill human melanoma cells efficiently and selectively, while being 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 (also known as INK4A or 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) protein family, as 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.
我们报告了一种合成的、能够穿透细胞的肽的鉴定，该肽能够有效地选择性地杀死人类黑色素瘤细胞，而对正常的人类黑素细胞的毒性较小，对人类成纤维细胞则没有毒性。该肽基于黑色素瘤抑制因子和衰老效应因子 p16（也称为 INK4A 或 CDKN2A）的靶结合位点，与穿透细胞部分相连。杀伤是通过细胞凋亡发生的，其作用途径似乎不同于 p16 和 CDK4 的经典下游靶标视网膜母细胞瘤 (RB) 蛋白家族，因为它在缺乏任何活性 RB 的 HeLa 细胞和表达 HPV E7 致癌基因的黑素细胞系中也同样有效。对其他类型的癌细胞系（如神经胶质瘤）的毒性不同。以前曾报道过 p16 衍生肽对黑色素瘤细胞的杀伤作用，但仅在较高浓度下，而选择性和普遍性以前未经过测试。
