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Down‐regulating Proteolysis to Enhance Anticancer Activity of Peptide Nanofibers
Author(s) -
Li Jie,
Du Xuewen,
Powell Devon J.,
Zhou Rong,
Shi Junfeng,
He Hongjian,
Feng Zhaoqianqi,
Xu Bing
Publication year - 2018
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.201800875
Subject(s) - proteolysis , peptide , nanofiber , hela , proteasome , cancer cell , intracellular , cytotoxicity , chemistry , bortezomib , cancer , biochemistry , microbiology and biotechnology , cell , biology , in vitro , materials science , nanotechnology , enzyme , immunology , genetics , multiple myeloma
Nanofibers of short peptides are emerging as a promising type of agents for inhibiting cancer cells. But the proteolysis of peptides decreases the anticancer efficacy of the peptide nanofibers. Here we show that decreasing the activity of proteasomes enhance the activity of peptide nanofibers for inhibiting cancer cells. Based on the structure of galactin‐3, we designed a heptapeptide, which self‐assembles to form nanofibers. The nanofibers of the heptapeptide exhibit moderate cytotoxicity to three representative cancer cell lines (HeLa, MCF‐7, and HepG2), largely due to the proteolysis of the peptides. Using a clinically approved proteasome inhibitor, bortezomib, to treat the cancer cells significantly decreases the proteolysis of the peptides and enhances the activity of the peptide nanofibers for inhibiting the cancer cells. This work illustrates a promising approach for enhancing the anticancer efficacy of peptide nanofibers by modulating intracellular protein degradation machinery, as well as provides insights for understanding the cytotoxicity of aberrant protein or peptide aggregates in complicated cellular environment.