In vitro investigation of cytotoxicity and apoptosis induction of hepcidin (TH1-5) on human breast cancer cell line MCF-7
Hepcidins are cysteine-rich antimicrobial peptides that have been identified from various fish species. Hepcidin (THI-5) have been isolated from freshwater tilapia fish Oreochromis mossambicus. Synthetic isoform of this peptide was previously reported for its antimicrobial, anti-inflammatory, wound-...
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| Format: | Thesis Book |
| Language: | English |
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| Summary: | Hepcidins are cysteine-rich antimicrobial peptides that have been identified from various fish species. Hepcidin (THI-5) have been isolated from freshwater tilapia fish Oreochromis mossambicus. Synthetic isoform of this peptide was previously reported for its antimicrobial, anti-inflammatory, wound-healing and cytotoxic functions. Its cytotoxic activities have been studied against human cancer cell lines including cervical, hepatocellular and fibrosarcoma cells. This study aims to investigate the potential cytotoxicity of the hepcidin (THI-5) synthetic peptide on human breast cancer cell line MCF-7. Cell viability was examined using the 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide (MTT) assay. Mode of cell death was determined via the acridine orange-propidium iodide double staining technique as well as annexin VFITC apoptotic assay. Apoptosis mechanisms through caspase activation from hepcidin (THI-5) induction was also analysed. Results showed the peptide to exert cytotoxic effect with a half maximal inhibitory concentration (ICso) of 20 ug/ml, but less cytotoxic to normal mouse embryonic fibroblast cells NIH/3T3. Fluorescence microscopy for mode of cell death revealed majority of the cell underwent apoptotic cell death after 24, 48 and 72 hours of treatment. The peptide also demonstrated increased caspase (caspase-317 and caspase-9) enzymatic activity and activate the mitochondrial intrinsic pathway of apoptosis. These results suggest that hepcidin (TH 1- 5) possess cytotoxic properties and induce apoptosis via the intrinsic pathway. In addition to its role in iron homeostasis, hepcidin can be developed as a potential chemotherapeutic candidate for breast cancer therapy. |
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| Physical Description: | xv, 101 leaves: illustration (some color); 30 cm. |
| Bibliography: | Includes bibliographical references (leaves 83-99) |