MRC Career award

MRC Career award

Apoptosis: A target for anti-cancer drug development.

Apoptosis is a highly regulated form of programmed cell death. Genes that regulate apoptosis are often mutated in malignant cells resulting in uncontrolled cell growth and the development of cancer. Numerous anti-cancer therapeutic approaches work by directly or indirectly activating apoptosis and subsequently destroying the cancer cells. However, drug resistance and drug selectivity remain big obstacles in anti-cancer drug development. TRAIL (Tumour necrosis factor-related apoptosis inducing factor) is emerging as a very promising pro-apoptotic anti-cancer agent. What makes TRAIL an attractive option as a potential anti-cancer drug is the fact that TRAIL specifically targets transformed cells and has little effect on normal cells. However, certain cancer types, including leukaemia are resistant to TRAIL. The combined treatment of TRAIL and arsenic trioxide can sensitize leukaemia cells to the effects of TRAIL. Part of my postdoctoral research at the National Centre for Biomedical Engineering Science (National University of Ireland, Galway), was to explore the potential use of arsenic trioxide to sensitize leukaemia cells to TRAIL and to delineate the possible mechanism of this effect.

His current research focus at the University of the Western Cape involves the evaluation of various Southern African medicinal plants for the presence of anti-tumour and pro-apoptotic bioactivity. Historically, many anti-cancer drugs, such as taxol, vinblastine and vincristine, originated from plants. They have identified three secondary metabolites from Tulbaghia violacea with potent pro-apoptotic activity and are currently investigating the mechanism by which these complexes activate apoptosis.