Ascorbic acid and ascorbate-2-phosphate decrease HIF activity and malignant properties of human melanoma cells
Posted: Sun Sep 17, 2017 5:40 pm
Article information
BMC Cancer. 2015; 15: 867.
Published online 2015 Nov 7. doi: 10.1186/s12885-015-1878-5
Conclusion
Our studies suggest a positive role for ascorbic acid in regulating HIF-1α in melanoma. The addition of ascorbic acid can effectively reduce the amount of stabilized HIF-1α found under normoxic conditions in both vertical growth phase WM1366 and WM9 metastatic melanoma cells. The addition of ascorbic acid also significantly reduces the transcriptional activity of HIF-1α in WM9 metastatic melanoma cells, resulting in decreased invasive potential. Our data supports the function of AA as a critical cofactor for PHD, restoring PHD function to reduce protein accumulation, and likely FIH activity resulting in significant reduction of HIF-1α transcriptional activity. However, there may also be non-PHD mediated mechanisms by which AA reduces the level of the HIF-1α protein. The overexpression of intra-tumor HIF-1α, as well as ascorbic acid deficiency has been noted not only in melanoma, but in other tumor types as well. Further studies to evaluate the causes of ascorbic acid deficiency and its role in the loss of HIF-1α regulation in malignancy are needed. The use of ascorbic acid as a non-toxic adjuvant therapy to aid in the inhibition of HIF-1α activity in order to reduce tumor progression and improve patient response to clinical therapy warrants further investigation.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4636772/
BMC Cancer. 2015; 15: 867.
Published online 2015 Nov 7. doi: 10.1186/s12885-015-1878-5
Conclusion
Our studies suggest a positive role for ascorbic acid in regulating HIF-1α in melanoma. The addition of ascorbic acid can effectively reduce the amount of stabilized HIF-1α found under normoxic conditions in both vertical growth phase WM1366 and WM9 metastatic melanoma cells. The addition of ascorbic acid also significantly reduces the transcriptional activity of HIF-1α in WM9 metastatic melanoma cells, resulting in decreased invasive potential. Our data supports the function of AA as a critical cofactor for PHD, restoring PHD function to reduce protein accumulation, and likely FIH activity resulting in significant reduction of HIF-1α transcriptional activity. However, there may also be non-PHD mediated mechanisms by which AA reduces the level of the HIF-1α protein. The overexpression of intra-tumor HIF-1α, as well as ascorbic acid deficiency has been noted not only in melanoma, but in other tumor types as well. Further studies to evaluate the causes of ascorbic acid deficiency and its role in the loss of HIF-1α regulation in malignancy are needed. The use of ascorbic acid as a non-toxic adjuvant therapy to aid in the inhibition of HIF-1α activity in order to reduce tumor progression and improve patient response to clinical therapy warrants further investigation.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4636772/