Antimicrobial cyclic decapeptides with anticancer activity

作者：Feliu Lidia; Oliveras Gloria; Cirac Anna D; Besalu Emili; Roses Cristina; Colomer Ramon; Bardaji Eduard; Planas Marta^*; Puig Teresa

来源：Peptides, 2010, 31(11): 2017-2026.

DOI：10.1016/j.peptides.2010.07.027

• Apoptosis
• Cervical carcinoma
• Cyclopeptides
• Pharmacological synergism
• Design of experiments

Antimicrobial peptides have been considered as potential candidates for cancer therapy We report here the cytotoxicity of a library of 66 antibacterial cyclodecapeptides on human carcinoma cell lines and their effects on apoptosis [as assessed by cleavage of poly(ADP-ribose) polymerase (PARP)] and cell signaling proteins (p53 and ERK1/2) in cultured human cervical carcinoma cells A design of experiments approach permitted to analyze the results of a subset of 16 peptides and define rules for high anticancer activity against MDA-MB-231 breast carcinoma cells Eight peptides were identified with IC(50) values ranging from 18 5 to 57 5 mu M against the five cell lines tested being HeLa cells the most sensitive Among these sequences BPC88 BPC96 BPC98 and BPC194 displayed specificity and high cytotoxicity against HeLa cells (IC(50) of 22 5-385 mu M) showed low hemolytic activity and low cytotoxicity to non-malignant fibroblasts and were stable to proteases in human serum Induction of apoptosis by these peptides was observed and the apoptotic effect of BPC88 and BPC96 caused a marked decrease on the activated form of ERK1/2 kinase and an induction of p53 We further showed that BPC96 at low doses synergized the

• 出版日期2010-11