Inhibiting Tumor Growth with Vitamin C

The conventional knowledge of how antioxidants such as vitamin C help prevent cancer growth is that they capture volatile oxygen free radical molecules and prevent the damage they are known to do to fragile DNA. However, the study, led by Chi Dang, M.D., Ph.D., professor of medicine and oncology and oncology research, from Johns Hopkins University (Baltimore, MD, USA), unexpectedly found that the antioxidants' actual role may be to destabilize a tumor's ability to grow under oxygen-starved conditions. Their study was detailed in the September 2007 issue of the journal Cancer Cell.

"The potential anticancer benefits of antioxidants have been the driving force for many clinical and preclinical studies,” noted Dr. Dang. "By uncovering the mechanism behind antioxidants, we are now better suited to maximize their therapeutic use. Once again, this work demonstrates the irreplaceable value of letting researchers follow their scientific noses wherever it leads them.”

The investigators, however, cautioned that while vitamin C is still necessary for good health, this study is preliminary and people should not run out and buy bulk supplies of antioxidants as a means of cancer prevention.

The Johns Hopkins investigators discovered the unexpected antioxidant mechanism while looking at mice implanted with either human lymphoma or human liver cancer cells. Both of these cancers produce high levels of free radicals that could be suppressed by feeding the mice supplements of antioxidants, either vitamin C or N-acetylcysteine (NAC).

However, when the researchers examined cancer cells from cancer-implanted mice not fed the antioxidants, they observed the absence of any significant DNA damage. "Clearly, if DNA damage was not in play as a cause of the cancer, then whatever the antioxidants were doing to help was also not related to DNA damage,” stated Ping Gao, Ph.D, lead author of the study.

This conclusion led Drs. Gao and Dang to suspect that another process was involved, such as a protein known to be dependent on free radicals called HIF-1 (hypoxia-induced factor), which was discovered over 10 years ago by Hopkins researcher and co-author Gregg Semenza, M.D., Ph.D., director of the Program in Vascular Cell Engineering. Indeed, they found that while this protein was abundant in untreated cancer cells taken from the mice, it disappeared in vitamin C-treated cells taken from similar animals.

"When a cell lacks oxygen, HIF-1 helps it compensate,” explained Dr. Dang. "HIF-1 helps an oxygen-starved cell convert sugar to energy without using oxygen and also initiates the construction of new blood vessels to bring in a fresh oxygen supply.”

Various rapidly growing tumors consume enough energy to easily suck out the available oxygen in their surrounding area, making HIF-1 extremely important for their continued survival. But HIF-1 can only work if it has a supply of free radicals. Antioxidants remove these free radicals and block HIF-1 and the tumor.

The investigators confirmed the importance of this "hypoxia protein” by creating cancer cells with a genetic variant of HIF-1 that did not require free radicals to be stable. In these cells, antioxidants no longer had any cancer-fighting abilities.


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