Abstract
M.Sc.
The ideal cancer treatment modality should not only cause tumour regression and eradication but also induce a systemic antitumour response, which is essential for the control of metastatic tumours and long-term tumour resistance. Photodynamic Therapy (PDT) is a current approach in the treatment of various cancers. It involves the administration of a tumour-localizing photoreactive compound, which is activated at a specific wavelength of light. This therapy results in a sequence of photochemical and photobiological processes that cause irreversible photodamage to tumour tissues. Eradication is achieved by anti-tumour effects induced in the parenchyma and tumour vascular network. PDT can lead to a rapid cell death response in malignant cells, which has provided insight into the mechanisms behind photokilling.
Oesophageal cancer is the seventh leading cause of cancer death worldwide, and in South Africa remains a problem of epidemic proportions affecting predominantly black males.
The appearance of a number of new photosensitizers being developed will not only extend the number of choices for treating specific cancers, but also aid in the effective destruction of various tumour tissues. PDT has been an experimental clinical modality for the past two xii
decades and has been shown to be successful for the treatment of advanced oesophageal cancer where other options have failed. The full potential of PDT as a treatment modality has not been clearly evaluated, which is one of the objectives of this study. Overall, PDT has the potential of being a promising therapeutic option in the effective treatment of oesophageal cancer, and through this study and the elucidation of the mechanisms of PDT action, it will provide a better future for those suffering from oesophageal cancer.
A new photosensitizer known as Zinc Sulphophthalo-cyanine (ZnPcSmix) was studied on an oesophageal SNO cancer cell line in order to determine treatment-induced cell viability, cytotoxicity and the pathway followed to cell death. The major observations of this study revealed that PDT using ZnPcSmix resulted in a decrease in cell viability and proliferation, resulting in a cytotoxic response experienced by the cell.
The outcome of this study revealed that the SNO cells experience a necrotic mode of cell death after using ZnPcSmix to induce photodamage. This was examined by light microscopy and confirmed by the lack of DNA fragmentation and decreased caspase-3 and caspase-7 expression levels. Hsp70 levels decreased resulting in lowered cytokine TNF-α release from necrotic cells. Hoechst nuclear staining revealed a disorganized nuclear pattern characteristic of necrotic release of cellular contents.
The major findings of this study revealed the efficacy of ZnPcSmix as a new photosensitizing drug used during PDT to treat oesophageal cancer resulting in a decrease in cell viability and proliferation. Necrosis was the primary mechanism by which cells pursued death, which was dependent on the photosensitizer dose, cell type and irradiation fluence. ZnPcSmix–induced photodamage seen during PDT offers a new treatment option for patients suffering from oesophageal cancer and shows great promise in effectively treating early-stage oesophageal cancer.