Repurposing an antimicrobial arginine-rich decapeptide as a novel anticancer agent: Evidence from in vitro and in vivo breast cancer models

Chamani, Reyhane; Mohammadi, Maryam

doi:10.22038/ijbms.2026.92237.19905

Repurposing an antimicrobial arginine-rich decapeptide as a novel anticancer agent: Evidence from in vitro and in vivo breast cancer models

Articles in Press

Document Type : Original Article

Authors

Department of Biology, Yazd University, Yazd, Iran

10.22038/ijbms.2026.92237.19905

Abstract

Objective(s): Arginine-rich peptides have attracted interest because of their ability to interact with negatively charged cancer cell membranes. The present study aimed to evaluate the anticancer properties of a novel antimicrobial arginine-rich decapeptide (RL10) in vitro and in vivo.
Materials and Methods: Cytotoxicity was assessed in breast (4T1), colon (SW480), and normal fibroblast (NIH3T3) cell lines by MTT assay following 48- and 72-hr treatment (6-400 µg/ml). Membrane integrity was examined in 4T1 cells after 48 hr using lactate dehydrogenase (LDH) release. Flow cytometry was applied to determine apoptosis induction and alterations in cell cycle distribution. Caspase 3/7 activity was also evaluated. Apoptosis-related gene expressions were analyzed using RT-PCR. The antitumor effect of RL10 was assessed in a murine 4T1 model, followed by histopathological analysis using H&E staining.
Results: RL10 significantly declined cancer cell viability in a dose-dependent manner, with no toxicity on normal cells. No increase in LDH release was detected. Flow cytometry revealed 28.9% apoptosis induction and cell cycle arrest at the S and G2/M phases. Marked upregulation of the Casp9 gene suggested possible activation of the intrinsic apoptotic pathway; however, Bax, Bcl2, p53, and Casp8 expressions remained unchanged. In vivo, two weeks’ treatment with the peptide suppressed tumor growth by nearly 39% (P˂0.01), accompanied by increased apoptotic figures and reduced mitotic counts.
Conclusion: These findings provide the first evidence that an arginine-rich short peptide exhibits anticancer activity through apoptosis induction and tumor growth inhibition, underscoring its potential as a candidate for cancer therapy or drug delivery systems.

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