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

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 (RL۱۰) in vitro and in vivo. Materials and Methods: Cytotoxicity was assessed in breast (۴T۱), colon (SW۴۸۰), and normal fibroblast (NIH۳T۳) cell lines by MTT assay following ۴۸- and ۷۲-hr treatment (۶-۴۰۰ µg/ml). Membrane integrity was examined in ۴T۱ cells after ۴۸ hr using lactate dehydrogenase (LDH) release. Flow cytometry was applied to determine apoptosis induction and alterations in cell cycle distribution. Caspase ۳/۷ activity was also evaluated. Apoptosis-related gene expressions were analyzed using RT-PCR. The antitumor effect of RL۱۰ was assessed in a murine ۴T۱ model, followed by histopathological analysis using H&E staining.Results: RL۱۰ 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 ۲۸.۹% apoptosis induction and cell cycle arrest at the S and G۲/M phases. Marked upregulation of the Casp۹ gene suggested possible activation of the intrinsic apoptotic pathway; however, Bax, Bcl۲, p۵۳, and Casp۸ expressions remained unchanged. In vivo, two weeks’ treatment with the peptide suppressed tumor growth by nearly ۳۹% (P˂۰.۰۱), 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.

کلیدواژه ها:

Antineoplastic agents ، Apoptosis ، Cell cycle/drug effects ، Dual-function peptide ، Peptides/chemistry