Novel in silico-designed SMYD3 inhibitors eliminate unrestrained proliferation of breast carcinoma cells
| dc.contributor.author | Alshiraihi, Ilham Mohammed, author | |
| dc.contributor.author | Brown, Mark, advisor | |
| dc.contributor.author | Kato, Takamitsu, advisor | |
| dc.contributor.author | Reynolds, Melissa, committee member | |
| dc.contributor.author | Snow, Christopher, committee member | |
| dc.date.accessioned | 2021-09-06T10:26:26Z | |
| dc.date.available | 2021-09-06T10:26:26Z | |
| dc.date.issued | 2021 | |
| dc.description.abstract | SMYD3 is a lysine methyltransferase that regulates the expression of over 80 genes and is required for the uncontrolled proliferation of most breast, colorectal, and hepatocellular carcinomas. Elimination of SMYD3 restores normal expression patterns of these genes and halts aberrant cell proliferation. In this study, we used in silico screening to identify potential small molecule inhibitors of SMYD3 and tested the ability of these inhibitors to reduce its methyltransferase activity in vitro. Using breast cancer cell lines that overexpress SMYD3 and normal breast epithelial cell lines, we have confirmed the ability of one of these inhibitors, Inhibitor-4, to reduce cell proliferation, arrest the cell cycle, and induce apoptosis in breast cancer cells without affecting normal cell behavior. Our results provide a proof of concept for the in silico design of small molecule enzyme inhibitors and for the use of such an inhibitor to target SMYD3 for the treatment of cancer. | |
| dc.format.medium | born digital | |
| dc.format.medium | doctoral dissertations | |
| dc.identifier | Alshiraihi_colostate_0053A_16711.pdf | |
| dc.identifier.uri | https://hdl.handle.net/10217/233827 | |
| dc.language | English | |
| dc.language.iso | eng | |
| dc.publisher | Colorado State University. Libraries | |
| dc.relation.ispartof | 2020- | |
| dc.rights | Copyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright. | |
| dc.title | Novel in silico-designed SMYD3 inhibitors eliminate unrestrained proliferation of breast carcinoma cells | |
| dc.type | Text | |
| dcterms.rights.dpla | This Item is protected by copyright and/or related rights (https://rightsstatements.org/vocab/InC/1.0/). You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). | |
| thesis.degree.discipline | Cell and Molecular Biology | |
| thesis.degree.grantor | Colorado State University | |
| thesis.degree.level | Doctoral | |
| thesis.degree.name | Doctor of Philosophy (Ph.D.) |
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