Anti-Proliferative Effects of Bioinspired Antimicrobial Peptides on MDA-MB-231 Triple- Negative Breast Cancer Cells

Conventional strategies for treating breast cancer, including chemotherapy and radiotherapy, often face critical challenges such as severe adverse effects and the development of therapeutic resistance. These limitations have driven interest in exploring alternative and complementary approaches with improved safety profiles and targeted efficacy. Among these, antimicrobial peptides (AMPs), naturally occurring components of the innate immune system, are increasingly recognized for their selective cytotoxic activity against cancer cells and potential immunomodulatory effects.In particular, AMPs derived from extremophiles—organisms adapted to survive in extreme environmental conditions—present compelling therapeutic opportunities. These peptides tend to exhibit remarkable stability and enzymatic resistance, which enhances their functionality under physiological conditions. Compared to plant-derived defensins, which may suffer from poor bioavailability despite their cysteine-rich profiles, and bacterial or synthetic AMPs, which can present selectivity or toxicity issues, extremophile-inspired peptides offer a more robust and targeted anticancer profile.In this study, bioinspired short antimicrobial peptides (BSAMPs) were designed in silico using structural motifs from extremophilic organisms to enhance anticancer activity and tumor specificity. When tested on MDA-MB-231 triple-negative breast cancer (TNBC) cells, BSAMPs significantly reduced cell viability (by 70% at 400 µg/ml), inhibited cellular migration (by 80%), and decreased invasion (by 60%), while showing minimal toxicity (≤ 10%) to non-malignant fibroblasts and MCF10A epithelial cells. Mechanistically, BSAMPs promoted apoptosis via mitochondrial pathways, downregulating β-catenin and Bcl-xl while increasing Bax expression. While these results are currently limited to in vitro models, they highlight the therapeutic potential of BSAMPs and justify further validation in in vivo systems for breast cancer treatment.