Open AccessNovel peptide dermaseptin‐ PS 1 exhibits anticancer activity via induction of intrinsic apoptosis signalling
Author(s) -
Long Qilin,
Li Lei,
Wang Hao,
Li Miaoran,
Wang Lei,
Zhou Mei,
Su Qiaozhu,
Chen Tianbao,
Wu Yuxin
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.14032
Subject(s) - apoptosis , frog skin , antimicrobial peptides , antimicrobial , cancer cell , in vitro , microbiology and biotechnology , cell , peptide , programmed cell death , mitochondrion , chemistry , biology , signal transduction , cancer , biochemistry , genetics , organic chemistry , sodium
Antimicrobial peptides ( AMP ) secreted by the granular glands of frog skin have been widely reported to exhibit strong bacteriostatic and bactericidal activities. Many of them have been documented with potent antiproliferative effects on multiple cancer cells, many studies also suggested that AMP s exert their functions via disrupting cell membranes. However, whether and how other cell death induction mechanism is involved in mammalian cancer cells has rarely been investigated. In this study, a novel AMP named Dermaseptin‐ PS 1 was isolated and identified from Phyllomedusa sauvagei , it showed strong antimicrobial activities against three types of microorganisms. In vitro antiproliferative studies on human glioblastoma U‐251 MG cells indicated that Dermaseptin‐ PS 1 disrupted cell membranes at the concentrations of 10 −5 M and above, while the cell membrane integrity was not affected when concentrations were decreased to 10 −6 M or lower. Further examinations revealed that, at the relatively low concentration (10 −6 M), Dermaseptin‐ PS 1 induced apoptosis through mitochondrial‐related signal pathway in U‐251 MG cells. Thus, for the first time, we report a novel frog skin derived AMP with anticancer property by distinct mechanisms, which largely depends on its concentration. Together, our study provides new insights into the mechanism‐illustrated drug design and the optimisation of dose control for cancer treatment in clinic.