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Wnt Signaling Pathway Collapse upon β-Catenin Destruction by a Novel Antimicrobial Peptide SKACP003: Unveiling the Molecular Mechanism and Genetic Activities Using Breast Cancer Cell Lines. | LitMetric

AI Article Synopsis

  • Metastatic breast cancer remains challenging to treat due to drug resistance and a lack of targeted therapies, but the antimicrobial peptide SKACP003 shows promise in inhibiting breast cancer cell growth.* -
  • SKACP003 disrupts the cell cycle and triggers apoptosis in various breast cancer cell lines by altering key gene expressions, decreasing BCL-2, and increasing pro-apoptotic markers like BAX and caspases.* -
  • The peptide also reduces the activity of the β-Catenin signaling pathway, which is linked to cancer progression, indicating its potential as a targeted treatment option for breast cancer.*

Article Abstract

Despite progress in breast cancer treatment, the survival rate for patients with metastatic breast cancer remains low due to chemotherapeutic agent resistance and the lack of specificity of the current generation of cancer drugs. Our previous findings indicated that the antimicrobial peptide SKACP003 exhibited anticancer properties, particularly against the MCF-7, MDA-MB-231, and MDA-MB-453 breast cancer cell lines. However, the mechanism of SKACP003-induced cancer cell death is unknown. Here, we investigated the molecular mechanism by which SKACP003 inhibits the cell cycle, cell proliferation, and angiogenesis in breast cancer cell lines. The results revealed that all the breast cancer cell lines treated at their IC values significantly inhibited the replicative phase of the cell cycle. The SKACP003-induced growth inhibition induced apoptosis, as evidenced by a decrease in BCL-2 and an increase in BAX and caspase gene (Cas-3, Cas-8, and Cas-9) expression. Reduced expression of the β-Catenin signaling pathway was associated with the SKACP003-induced apoptosis. SKACP003-treated breast cancer cells showed decreased expression of Wnt/β-Catenin targeting genes such as C-Myc, P, and COX-2 and significant downregulation of CDK-4 and CDK-6 genes. Furthermore, cytoplasmic β-catenin protein levels in SKACP003-treated cell lines were significantly lower than in control cell lines. The results of the current study suggest that the newly identified antimicrobial peptide SKACP003 has great potential as a candidate for specifically targeting the β-catenin and thus significantly reducing the progression and prognosis of breast cancer cell lines.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9920962PMC
http://dx.doi.org/10.3390/molecules28030930DOI Listing

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