| Summary: | The current treatment for cancer is focused on chemotherapeutic treatments which can lead to many side effects including nausea, vomiting and chemoresistance. Combating chemoresistance is a key target in cancer therapy, along with enhancing the effects of current chemotherapy treatments. One progressive novel approach being investigated is pre-treating (“priming”) cells prior to chemotherapeutic treatment. Evidence has shown that “priming” of cancer cells can sensitizes the mitochondria to respond better to chemotherapy and hence reduce severity of treatment and side effects. In this thesis, I aim to define the mechanism by which “priming” enhances cell death through the mitochondria. Firstly, cannabidiol (CBD), a phytocannabinoid that has shown to have beneficial properties in inflammation, pain relief and in reducing cancer cell progression was examined for a potential “priming” agent. Secondly, the effect of the chemotherapy agent, cisplatin, was fully defined for its role in mitochondrial function along with a combination therapy of CBD and cisplatin. And finally, “priming” with CBD was assessed for any potential benefit to cancer treatment. I have demonstrated here that “priming” with CBD can enhance the killing effect of cisplatin in cancer cells and not in control cells. More specifically, the underlying mechanism for “priming” by CBD was shown to be through the modulation of mitochondrial function by means of the high stress two-phase system p53/Nrf2 together with voltage dependant anion channel 1 (VDAC1) receptor activation. From this body of work, “priming” has been shown to have a potential in enhancing current chemotherapeutic treatment.
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