Antimicrobial Peptide Brevinin-1RL1 from Frog Skin Secretion Induces Apoptosis and Necrosis of Tumor Cells
| Autor: | Xiaoman Ju, Dongmei Fan, Shaohua Zhang, Ling-Mei Kong, Yiying Zhu, Yan Li, Qihong Yang, Guifeng Su |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Pore Forming Cytotoxic Proteins
Necrosis antimicrobial peptide Ranidae caspase Antimicrobial peptides Pharmaceutical Science Apoptosis anticancer Hemolysis Article Analytical Chemistry lcsh:QD241-441 Brevivin-1RL1 03 medical and health sciences Inhibitory Concentration 50 Protein Aggregates 0302 clinical medicine lcsh:Organic chemistry Cell Line Tumor Drug Discovery medicine Animals Secretion Viability assay Amino Acid Sequence Physical and Theoretical Chemistry Caspase 030304 developmental biology Skin 0303 health sciences biology Chemistry Organic Chemistry Intrinsic apoptosis Molecular Weight Chemistry (miscellaneous) 030220 oncology & carcinogenesis Caspases Cancer cell biology.protein Cancer research Molecular Medicine medicine.symptom |
| Zdroj: | Molecules Molecules, Vol 26, Iss 2059, p 2059 (2021) Volume 26 Issue 7 |
| ISSN: | 1420-3049 |
| Popis: | Cancer has always been one of the most common malignant diseases in the world. Therefore, there is an urgent need to find potent agents with selective antitumor activity against cancer cells. It has been reported that antimicrobial peptides (AMPs) can selectively target tumor cells. In this study, we focused on the anti-tumor activity and mechanism of Brevinin-1RL1, a cationic α-helical AMP isolated from frog Rana limnocharis skin secretions. We found that Brevinin-1RL1 preferentially inhibits tumor cells rather than non-tumor cells with slight hemolytic activity. Cell viability assay demonstrated the intermolecular disulfide bridge contributes to the inhibitory activity of the peptide as the antitumor activity was abolished when the disulfide bridge reduced. Further mechanism studies revealed that both necrosis and apoptosis are involved in Brevinin-1RL1 mediated tumor cells death. Moreover, Brevinin-1RL1 induced extrinsic and mitochondria intrinsic apoptosis is caspases dependent, as the pan-caspase inhibitor z-VAD-FMK rescued Brevinin-1RL1 induced tumor cell proliferative inhibition. Immunohistology staining showed Brevinin-1RL1 mainly aggregated on the surface of the tumor cells. These results together suggested that Brevinin-1RL1 preferentially converges on the cancer cells to trigger necrosis and caspase-dependent apoptosis and Brevinin-1RL1 could be considered as a pharmacological candidate for further development as anti-cancer agent. |
| Databáze: | OpenAIRE |
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