Down-regulating Proteolysis to Enhance Anticancer Activity of Peptide Nanofibers

Area of Science:

• Biomaterials Science
• Cancer Biology
• Molecular Medicine

Background:

• Short peptide nanofibers are investigated as potential anticancer agents.
• Peptide degradation via proteolysis reduces the efficacy of these nanofibers.
• Targeting intracellular protein degradation pathways offers a novel therapeutic strategy.

Purpose of the Study:

• To investigate the effect of proteasome inhibition on the anticancer activity of peptide nanofibers.
• To design and synthesize peptide nanofibers based on galectin-3 structure.
• To evaluate the cytotoxicity of these nanofibers and the impact of proteasome activity on their performance.

Main Methods:

• Design of a heptapeptide based on galectin-3 structure.
• Self-assembly of the heptapeptide into nanofibers.
• Assessment of cytotoxicity against HeLa, MCF-7, and HepG2 cancer cell lines.
• Treatment with bortezomib (a proteasome inhibitor) to modulate proteasome activity.

Main Results:

• The designed heptapeptide self-assembles into nanofibers.
• These peptide nanofibers exhibit moderate cytotoxicity, partly due to proteolysis.
• Inhibition of proteasomes with bortezomib significantly reduced peptide degradation.
• Proteasome inhibition markedly enhanced the anticancer efficacy of the peptide nanofibers.

Conclusions:

• Decreasing proteasome activity enhances the anticancer efficacy of peptide nanofibers.
• Modulating intracellular protein degradation machinery is a viable strategy to improve peptide nanofiber-based cancer therapies.
• This study provides insights into the cytotoxicity mechanisms of peptide aggregates in cellular environments.