Exploring the effects and efficacy of novel cell cycle regulating compounds in aggressive Breast, Ovarian and Cervical Cancer

The Spindle Assembly Checkpoint (SAC) is a cell signalling system that regulates cell division. SAC ensures the correct separation of chromosomes during mitosis. Defects in SAC can result in genome instability, increasing the risk of cancer development and making it a potential therapeutic target for cancer treatment. The commercial compounds Reversine (an Aurora kinase B and Mps1 inhibitor) and Apcin (an APC/C inhibitor) have been established to be cytotoxic to cancer. This thesis aimed to confirm the efficacy of these compounds and to test the cytotoxicity of three novel small molecules that interfere with cell cycle progression in cancer cells, ultimately inducing apoptosis (cell death). MTT and clonogenic assays were the techniques selected to test the cytotoxicity of the compounds in a cancer cell line panel. The cancer cell lines tested includes (b) Hormone responding breast cancer, MCF7 (c) Triple-Negative Hormone Resistant breast cancer, MDA-MB 231 (d) Ovarian cancer, SKOV3 (e) Cervical cancer, HeLa. Retinal Pigment The epithelial cell line RPE-1 was used as a control. Western blotting was used to investigate the expression levels of Cdc20 and Cyclin B1 to confirm the compounds were acting on the intended target. The novel compounds were found to reduce cell viability in the cancer cell lines tested but were also very cytotoxic to the non-carcinomic RPE-1 cells. The cytotoxicity experiments covered a large concentration range to calculate IC50 values via dose-response curves. The expression levels of Cyclin B1 and Cdc20 as monitored by western blot rendered variable results.

Grantor dc:publisher

Oxford Brookes University

Author dc:creator

• Rossi, Luca

Contributors dc:contributor

• Bolanos-Garcia, Victor

Statement dc:rights

• All rights reserved

Language dc:language

en

DOI dc:identifier

https://doi.org/10.24384/59h0-px43

OAI identifier oai:identifier

tle:e69a56b7-2fb2-4b3d-a10a-a93157fdad89:d6bd9758-527a-46cd-bfe2-c433766e8fca:1