Smith, Laura Caroline (2026) Exploring the Mechanisms underpinning the Increased anti-Cancer Efficacy of Apaziquone in Hypoxic in vitro Breast Cancer. Masters thesis, York St John University.
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Abstract
Apaziquone (EO9) is an indolequinone bio reductive drug which relies on the cytosolic enzyme NQO1 for the activation. However, alternative findings suggest enhanced efficacy under hypoxic even when NQO1 expression is low. The aims of this study were to investigate alternative activation mechanisms of EO9 under hypoxic conditions. In vitro assays were conducted on BT474 and T47D under normoxic and hypoxic conditions, measuring cell viability, drug efficacy, ROS production and the influence of NQO1 on EO9
activation. Under hypoxia, EO9 exhibited a markedly ncreased cytotoxicity as the ED50 for T47D cell decreased by approximately 200-fold, while BT474 cells showed a 100-fold
reduction. Notably, NQO1 activity was low in both cell lines, at 3.00 x10-3 μmol/mg/min in T47D and 6.74 x10-3 μmol/mg/min in BT474 cells, suggesting that EO9 activation under hypoxia may occur via alternative pathways such as ROS mediated mechanisms. These findings challenge the reliance on NQO1 for EO9 activation and support EO9’s use in hypoxic tumours with low NQO1 expression.
| Item Type: | Thesis (Masters) |
|---|---|
| Status: | Published |
| Subjects: | Q Science > Q Science (General) |
| School/Department: | School of Science, Technology and Health |
| URI: | https://ray.yorksj.ac.uk/id/eprint/15780 |
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