원문정보
초록
영어
Histonin is a novel cell-penetrating anticancer peptide derived from histone H2A. In this study, we analyzed the effects of this 21-amino acid peptide on a variety of cancer cell lines. Histonin displayed selective cytotoxicity against 62 cancer cell lines, with IC50 values (concentration of peptide at 50% cytotoxicity) in the 6 to 24 g/ml range. Histonin bound to cell surface gangliosides and sialic acids for penetration into cancer cells. Histonin penetrated cancer cell membranes
selectively without damaging them and accumulated primarily in the nuclei.
Once inside the cells, histonin bound to intracellular macromolecules, such as DNA, RNA, and heat shock proteins, and induced mitochondria-dependent apoptosis. In vivo analysis of histonin revealed that it reduced about 90% of the volume of a fibrosarcoma mass (a cancerous tumor of the fibrous connective tissue) in p53-deficient mice and killed almost all of the tumor cells. Moreover, histonin displayed remarkable tumor suppression activity in a mouse tumor xenograft model. The high selectivity of histonin for cancer cells as well as its ability to reduce the mass of established tumors and to suppress tumor formation suggests that histonin constitutes a novel therapeutic agent for the treatment of cancers.