Polyarginine and its analogues inhibit p53 mutant aggregation and cancer cell proliferation in vitro.

Abstract

Arginine, a cationic amino acid is known to stabilize proteins under harsh conditions. It is widely used to stabilize protein aggregation, and to correct protein folding during protein production. Hence it would be a good therapeutic candidate for treating protein aggregation related diseases. Recent reports suggest, that the aggregation of tumor suppressor protein p53 is one of the leading causes of tumor progression. When mutated, p53 protein aggregates, loses its function leading to unwanted cell growth and ultimately results in tumor. Here in this study we focus on the inhibitory effects of polyarginine and its analogues polyornithine, canavanine, and citrulline on the inhibition of p53 mutant peptide aggregation, and p53 mutant cancer cell proliferation inhibition in vitro. Biochemical assays and cell toxicity studies were used to characterize the study. The results show that polyarginine, and polyornithine, in micromolar concentrations, significantly inhibits p53 conserved peptide aggregation, and the cell proliferation of p53 mutant cancer cells. Hence they could be promising candidates for treating p53 mutant/misfolded protein aggregation associated cancer.

• Authors: Zhaolin Chen, Jun Chen, Venkateshwar G Keshamouni, Mathumai Kanapathipillai
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 489 Issue 2 Pg. 130-134 (07 22 2017) ISSN: 1090-2104 [Electronic] United States
• PMID: 28536076 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• Peptides
• Protein Aggregates
• Tumor Suppressor Protein p53
• polyarginine

Topics

• Antineoplastic Agents (administration & dosage, chemistry, pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• High-Throughput Screening Assays
• Humans
• Mutation
• Neoplasms (genetics, pathology)
• Peptides (administration & dosage, chemistry, pharmacology)
• Protein Aggregates (drug effects)
• Protein Aggregation, Pathological (drug therapy, pathology, prevention & control)
• Structure-Activity Relationship
• Tumor Suppressor Protein p53 (genetics, metabolism)