E-Thesis 258 views
Mechanistic insights into the anticancer effects of SUV39H2 inhibitor and Sulindac in ovarian cancer / Nicole Villella
Swansea University Author: Nicole Villella
Abstract
Ovarian cancer (OC) is the 6th most common cancer in women, the most lethal gynaecological cancer and commonly develops chemotherapeutic resistance and is linked with poor prognosis, therefore new approaches are needed.Non-steroidal-anti-inflammatory drugs (NSAIDs) and epigenetic drugs are emerging...
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Swansea, Wales, UK
2025
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| Institution: | Swansea University |
| Degree level: | Master of Research |
| Degree name: | MSc by Research |
| Supervisor: | Conlan, Steve |
| URI: | https://cronfa.swan.ac.uk/Record/cronfa69513 |
| Abstract: |
Ovarian cancer (OC) is the 6th most common cancer in women, the most lethal gynaecological cancer and commonly develops chemotherapeutic resistance and is linked with poor prognosis, therefore new approaches are needed.Non-steroidal-anti-inflammatory drugs (NSAIDs) and epigenetic drugs are emerging as potential anticancer treatments. Gaining mechanistic insights into a NSAID, Sulindac, and an epigenetic target, Suppressor of Variegation Homolog 2 (SUV39H2) inhibitor (OTS) in OC could aid both in the development of new effective treatments for OC. To characterise the mechanistic functions of SUV39H2 and Sulindac, we first performed viability assays and observed significant induced apoptosis, especially following combinatorial treatments of Sulindac and OTS. Furthermore, high-content imaging analysis of the nucleus showed that OTS may affect the cell cycle progression. mRNA expression levels of b catenin decreased following treatment with Sulindac. OTS led to inhibition of SUV39H2 histone modification sites, H3K9me2/me3 and inhibition of LSD1, which is found to be overexpressed in OC. Induction of ERb protein expression levels, a key tumour suppressor gene, in OC, in endometrial and breast cancer, is highly promising. RNA sequencing analysis following treatment with a LSD1 inhibitor and OTS found a panel of common upregulated and downregulated genes in OC cell lines and regulation of pathways and processes involved in cancer. Overall, Sulindac and OTS show to incorporate great potential as a combining treatment for OC. |
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| Keywords: |
ovarian cancer, epigenetics, NSAIDs, drug development, ER- beta |
| College: |
Faculty of Medicine, Health and Life Sciences |