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Mechanistic insights into the anticancer effects of SUV39H2 inhibitor and Sulindac in ovarian cancer / Nicole Villella

Swansea University Author: Nicole Villella

  • E-Thesis – open access under embargo until: 13th May 2030

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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Published: Swansea, Wales, UK 2025
Institution: Swansea University
Degree level: Master of Research
Degree name: MSc by Research
Supervisor: Conlan, Steve
URI: https://cronfa.swan.ac.uk/Record/cronfa69513
first_indexed 2025-05-14T14:07:33Z
last_indexed 2025-05-15T10:50:17Z
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recordtype RisThesis
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spelling 2025-05-14T15:12:52.2943015 v2 69513 2025-05-14 Mechanistic insights into the anticancer effects of SUV39H2 inhibitor and Sulindac in ovarian cancer ef33636b46413383d552176b8c8d6afe Nicole Villella Nicole Villella true false 2025-05-14 MEDS 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. E-Thesis Swansea, Wales, UK ovarian cancer, epigenetics, NSAIDs, drug development, ER- beta 13 5 2025 2025-05-13 COLLEGE NANME Medical School COLLEGE CODE MEDS Swansea University Conlan, Steve Master of Research MSc by Research 2025-05-14T15:12:52.2943015 2025-05-14T15:04:36.7938885 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science Nicole Villella 1 Under embargo Under embargo 2025-05-14T15:12:23.5814845 Output 6865568 application/pdf E-Thesis – open access true 2030-05-13T00:00:00.0000000 Copyright: The Author, Maria Nicole Villella, 2025. true eng
title Mechanistic insights into the anticancer effects of SUV39H2 inhibitor and Sulindac in ovarian cancer
spellingShingle Mechanistic insights into the anticancer effects of SUV39H2 inhibitor and Sulindac in ovarian cancer
Nicole Villella
title_short Mechanistic insights into the anticancer effects of SUV39H2 inhibitor and Sulindac in ovarian cancer
title_full Mechanistic insights into the anticancer effects of SUV39H2 inhibitor and Sulindac in ovarian cancer
title_fullStr Mechanistic insights into the anticancer effects of SUV39H2 inhibitor and Sulindac in ovarian cancer
title_full_unstemmed Mechanistic insights into the anticancer effects of SUV39H2 inhibitor and Sulindac in ovarian cancer
title_sort Mechanistic insights into the anticancer effects of SUV39H2 inhibitor and Sulindac in ovarian cancer
author_id_str_mv ef33636b46413383d552176b8c8d6afe
author_id_fullname_str_mv ef33636b46413383d552176b8c8d6afe_***_Nicole Villella
author Nicole Villella
author2 Nicole Villella
format E-Thesis
publishDate 2025
institution Swansea University
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Biomedical Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Biomedical Science
document_store_str 0
active_str 0
description 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.
published_date 2025-05-13T05:54:38Z
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score 11.109323

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