Anti-Cancer and Anti-Inflammatory Activities of a Short Molecule, PS14 Derived from the Virulent Cellulose Binding Domain of <i>Aphanomyces invadans</i>, on Human Laryngeal Epithelial Cells and an In Vivo Zebrafish Embryo Model
In this study, the anti-cancer and anti-inflammatory activities of PS14, a short peptide derived from the cellulase binding domain of pathogenic fungus, <i>Aphanomyces invadans</i>, have been evaluated, in vitro and in vivo. Bioinformatics analysis of PS14 revealed the physicochemical pr...
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| Format: | Article |
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MDPI AG
2022-10-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/21/7333 |
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| author | Manikandan Velayutham Purabi Sarkar Gokul Sudhakaran Khalid Abdullah Al-Ghanim Shahid Maboob Annie Juliet Ajay Guru Saravanan Muthupandian Jesu Arockiaraj |
| author_facet | Manikandan Velayutham Purabi Sarkar Gokul Sudhakaran Khalid Abdullah Al-Ghanim Shahid Maboob Annie Juliet Ajay Guru Saravanan Muthupandian Jesu Arockiaraj |
| author_sort | Manikandan Velayutham |
| collection | DOAJ |
| description | In this study, the anti-cancer and anti-inflammatory activities of PS14, a short peptide derived from the cellulase binding domain of pathogenic fungus, <i>Aphanomyces invadans</i>, have been evaluated, in vitro and in vivo. Bioinformatics analysis of PS14 revealed the physicochemical properties and the web-based predictions, which indicate that PS14 is non-toxic, and it has the potential to elicit anti-cancer and anti-inflammatory activities. These in silico results were experimentally validated through in vitro (L6 or Hep-2 cells) and in vivo (zebrafish embryo or larvae) models. Experimental results showed that PS14 is non-toxic in L6 cells and the zebrafish embryo, and it elicits an antitumor effect Hep-2 cells and zebrafish embryos. Anticancer activity assays, in terms of MTT, trypan blue and LDH assays, showed a dose-dependent inhibitory effect on cell proliferation. Moreover, in the epithelial cancer cells and zebrafish embryos, the peptide challenge (i) caused significant changes in the cytomorphology and induced apoptosis; (ii) triggered ROS generation; and (iii) showed a significant up-regulation of anti-cancer genes including BAX, Caspase 3, Caspase 9 and down-regulation of Bcl-2, in vitro. The anti-inflammatory activity of PS14 was observed in the cell-free in vitro assays for the inhibition of proteinase and lipoxygenase, and heat-induced hemolysis and hypotonicity-induced hemolysis. Together, this study has identified that PS14 has anti-cancer and anti-inflammatory activities, while being non-toxic, in vitro and in vivo. Future experiments can focus on the clinical or pharmacodynamics aspects of PS14. |
| first_indexed | 2024-03-09T18:49:08Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T18:49:08Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-9f21625efd414f409b97a1982fa05d762023-11-24T06:02:26ZengMDPI AGMolecules1420-30492022-10-012721733310.3390/molecules27217333Anti-Cancer and Anti-Inflammatory Activities of a Short Molecule, PS14 Derived from the Virulent Cellulose Binding Domain of <i>Aphanomyces invadans</i>, on Human Laryngeal Epithelial Cells and an In Vivo Zebrafish Embryo ModelManikandan Velayutham0Purabi Sarkar1Gokul Sudhakaran2Khalid Abdullah Al-Ghanim3Shahid Maboob4Annie Juliet5Ajay Guru6Saravanan Muthupandian7Jesu Arockiaraj8Department of Biotechnology, College of Science and Humanities, SRM Institute of Science and Technology, Chennai 603 203, Tamil Nadu, IndiaDepartment of Molecular Medicine, School of Allied Healthcare and Sciences, Jain Deemed-to-be University, Bangalore 560 066, Karnataka, IndiaDepartment of Biotechnology, College of Science and Humanities, SRM Institute of Science and Technology, Chennai 603 203, Tamil Nadu, IndiaDepartment of Zoology, College of Science, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Zoology, College of Science, King Saud University, Riyadh 11451, Saudi ArabiaInstitute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX 78712, USADepartment of Conservative Dentistry and Endodontics, Saveetha Dental College and Hospitals, SIMATS, Chennai 600 077, Tamil Nadu, IndiaAMR and Nanomedicine Lab, Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciencess (SIMATS), Chennai 600 077, Tamil Nadu, IndiaDepartment of Biotechnology, College of Science and Humanities, SRM Institute of Science and Technology, Chennai 603 203, Tamil Nadu, IndiaIn this study, the anti-cancer and anti-inflammatory activities of PS14, a short peptide derived from the cellulase binding domain of pathogenic fungus, <i>Aphanomyces invadans</i>, have been evaluated, in vitro and in vivo. Bioinformatics analysis of PS14 revealed the physicochemical properties and the web-based predictions, which indicate that PS14 is non-toxic, and it has the potential to elicit anti-cancer and anti-inflammatory activities. These in silico results were experimentally validated through in vitro (L6 or Hep-2 cells) and in vivo (zebrafish embryo or larvae) models. Experimental results showed that PS14 is non-toxic in L6 cells and the zebrafish embryo, and it elicits an antitumor effect Hep-2 cells and zebrafish embryos. Anticancer activity assays, in terms of MTT, trypan blue and LDH assays, showed a dose-dependent inhibitory effect on cell proliferation. Moreover, in the epithelial cancer cells and zebrafish embryos, the peptide challenge (i) caused significant changes in the cytomorphology and induced apoptosis; (ii) triggered ROS generation; and (iii) showed a significant up-regulation of anti-cancer genes including BAX, Caspase 3, Caspase 9 and down-regulation of Bcl-2, in vitro. The anti-inflammatory activity of PS14 was observed in the cell-free in vitro assays for the inhibition of proteinase and lipoxygenase, and heat-induced hemolysis and hypotonicity-induced hemolysis. Together, this study has identified that PS14 has anti-cancer and anti-inflammatory activities, while being non-toxic, in vitro and in vivo. Future experiments can focus on the clinical or pharmacodynamics aspects of PS14.https://www.mdpi.com/1420-3049/27/21/7333cellulase binding domainzebrafishvirulent moleculeanti-cancerant-inflammatory |
| spellingShingle | Manikandan Velayutham Purabi Sarkar Gokul Sudhakaran Khalid Abdullah Al-Ghanim Shahid Maboob Annie Juliet Ajay Guru Saravanan Muthupandian Jesu Arockiaraj Anti-Cancer and Anti-Inflammatory Activities of a Short Molecule, PS14 Derived from the Virulent Cellulose Binding Domain of <i>Aphanomyces invadans</i>, on Human Laryngeal Epithelial Cells and an In Vivo Zebrafish Embryo Model Molecules cellulase binding domain zebrafish virulent molecule anti-cancer ant-inflammatory |
| title | Anti-Cancer and Anti-Inflammatory Activities of a Short Molecule, PS14 Derived from the Virulent Cellulose Binding Domain of <i>Aphanomyces invadans</i>, on Human Laryngeal Epithelial Cells and an In Vivo Zebrafish Embryo Model |
| title_full | Anti-Cancer and Anti-Inflammatory Activities of a Short Molecule, PS14 Derived from the Virulent Cellulose Binding Domain of <i>Aphanomyces invadans</i>, on Human Laryngeal Epithelial Cells and an In Vivo Zebrafish Embryo Model |
| title_fullStr | Anti-Cancer and Anti-Inflammatory Activities of a Short Molecule, PS14 Derived from the Virulent Cellulose Binding Domain of <i>Aphanomyces invadans</i>, on Human Laryngeal Epithelial Cells and an In Vivo Zebrafish Embryo Model |
| title_full_unstemmed | Anti-Cancer and Anti-Inflammatory Activities of a Short Molecule, PS14 Derived from the Virulent Cellulose Binding Domain of <i>Aphanomyces invadans</i>, on Human Laryngeal Epithelial Cells and an In Vivo Zebrafish Embryo Model |
| title_short | Anti-Cancer and Anti-Inflammatory Activities of a Short Molecule, PS14 Derived from the Virulent Cellulose Binding Domain of <i>Aphanomyces invadans</i>, on Human Laryngeal Epithelial Cells and an In Vivo Zebrafish Embryo Model |
| title_sort | anti cancer and anti inflammatory activities of a short molecule ps14 derived from the virulent cellulose binding domain of i aphanomyces invadans i on human laryngeal epithelial cells and an in vivo zebrafish embryo model |
| topic | cellulase binding domain zebrafish virulent molecule anti-cancer ant-inflammatory |
| url | https://www.mdpi.com/1420-3049/27/21/7333 |
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