Abstract
The combination of frequent diagnoses and its status as the leading cause of cancer-related deaths worldwide makes lung cancer a major issue. Targeting the redox system, which regulates cellular homeostasis by balancing reduction and oxidation reactions, offers a potential therapeutic approach. Reactive oxygen species (ROS) are pro-oxidant molecules generated by oxygen metabolism that are key to the redox mechanism; once antioxidants are depleted, ROS production results in cellular damage. We hypothesise that, through the exploitation of ROS generated in the lung tumour cells, the pharmacological application of the organoselenium compounds diphenylselenide (DPS) and diphenyldiselenide (DPDS) will lead to imbalances in redox homeostasis, favouring tumour damage.
Cytotoxic effects of DPS, DPDS, and hydrogen peroxide (H2O2) were assessed using the MTT assay to establish baseline effects. Compounds decreased viability in a dose-dependent manner. Results displayed IC50 values of 74 μM, 290 μM, and 3.6 mM, respectively. Combinations of both the organoselenium compounds with H2O2 were then tested. This showed that the DPDS presented a more potent effect compared to DPS, with IC50 values of 3.1 mM compared to 3.7 mM, respectively. Once the anti-tumour effects were established, investigation into the potential mechanism of action examined cellular oxidation by labelling with the fluorescent H2DCFDA probe. The combination of DPS with H2O2 produced the highest fluorescence signal among the combination treatments and organoselenium compounds alone, which indicated a greater level of oxidative stress induced.
In conclusion, the findings of this thesis provide evidence supporting the use of the organoselenium compounds DPDS and DPS in lung cancer treatment, with DPDS proving to be more effective. The long-term significance will support the development of redox-targeted chemotherapeutic strategies using organoselenium compounds for the treatment of lung cancer.