A new role for Vitamin C:control of the hypoxic response in cancer cells
2007 Research Project Grant Round
Researcher 1 - Margreet Vissers
Free Radical Research Group
University of Otago, Christchurch
Amount funded: $69,851.00 over a 12 month period
$15,000 has been kindly donated by the WH Travis Trust
and $10,000 donation from the Bone Marrow Cancer Research Trust
towards funding this project.
Photo shows Margreet Vissers in the laboratory.
Researcher 1 - Margreet Vissers
University of Otago, Christchurch
Researcher 2 - Gabi Dachs
University of Otago, Christchurch
Specific Objective(s)/Aims for this research.
Many cancer cells survive because they can adapt to a low oxygen environment through the action of a transcription factor known as hypoxia-inducible factor (HIF)-1α, which is normally not present, but which appears when the oxygen supply is limited. HIF-1α regulates the production of new blood vessels and influences tumour growth and survival, making cancer cells resistant to chemotherapy.
We have previously found that intracellular Vitamin C (ascorbic acid, ascorbate) can influence HIF-1α, and its availability may prove to be important for cancer treatment. In this project we intend to investigate the effects of vitamin C on the regulation of HIF-1α in cultured tumour cells.
Specific objectives
The objectives of this project are to determine the effect of intracellular ascorbate on HIF-1α regulation and gene expression in tumour cells and on subsequent tumour cell survival. Our aims are:
1. To probe the role of intracellular ascorbate on the hypoxic response in cancer cells with and without ascorbate supplementation.
2. Using transiently transfected cells to monitor the expression of GFP-tagged reporter genes, and to measure levels of VEGF and GLUT-1 mRNA and protein.
3. To develop a Microarray assay to investigate the effect of intracellular ascorbate on HIF-1α-dependent gene expression more generally.
Link to Outcomes
HIF-1α influences cell survival and controlling it is vital for the successful treatment of cancer. Our experiments will provide information on the ability of intracellular vitamin C to moderate HIF-1α-mediated gene expression, which will affect the tumour’s susceptibility to chemotherapy and other anti-cancer treatments such as radiation.
