Novel Anti-Cancer Agents: Potential of Protease Enzymes from Vibrio alginolyticus as a Breast Cancer Therapy for MCF-7 Cells

Abstract

This study explores the potential of Vibrio alginolyticus protease enzyme as a cytotoxic agent against MCF-7 breast cancer cells, using molecular docking and cytotoxicity assays. The docking analysis revealed that the native ligand interacts strongly with key residues at the active site of the target protein, including hydrogen bonds with residues ARG394 (2.034 Å) and GLU353 (1.920 Å), as well as hydrophobic interactions with residues PHE404, LEU391, MET421, and ILE424, with distances ranging from 4.664 Å to 5.355 Å. These interactions demonstrate a high affinity between the ligand and the target protein, indicating potential for enzyme-based cancer therapy development. Cytotoxicity testing using the resazurin assay showed that V. alginolyticus protease enzyme exhibited an IC50 value of 1.63 μg/mL, indicating significant cytotoxic effects on MCF-7 cells. At concentrations above 2.5 μg/mL, the enzyme demonstrated strong cytotoxic effects, with morphological changes in the cells, such as shrinkage and detachment. In contrast, at lower concentrations, the cytotoxic activity was limited. The observed decrease in cell viability at high concentrations suggests that the enzyme works by disrupting key proteins or pathways involved in cancer cell proliferation and survival. Both in silico and in vitro analyses support the possibility that V. alginolyticus protease targets essential proteins involved in apoptosis regulation and structural protein degradation in cancer cells. These findings provide new insights into the development of enzyme-based cancer therapies, warranting further research to understand the specific mechanisms behind cancer cell death induction. HIGHLIGHTS Vibrio alginolyticus protease demonstrated strong binding affinity to MCF-7 breast cancer target proteins through molecular docking, showing key interactions at ARG394 and GLU353. Hydrophobic and hydrogen bond interactions between the protease and residues PHE404, LEU391, MET421, and ILE424 support its potential as a protein-targeting therapeutic. Cytotoxicity assays revealed a low IC50 value of 1.63 μg/mL, indicating potent cytotoxic effects against MCF-7 cells at relatively low concentrations. Both in silico and in vitro results suggest apoptosis regulation and structural protein degradation as possible mechanisms of cancer cell death induction by the enzyme. GRAPHICAL ABSTRACT

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