By depleting the supply of oxygen radicals, they prevent HIF-1’s ability to sustain tumor growth.
Johns Hopkins scientists found that in mice, vitamin C and some other antioxidants, indeed inhibit the growth of some tumors, but the mechanism differs from that previously suggested.
The conventional wisdom of how antioxidants help prevent cancer growth is that they grab volatile oxygen free radical molecules and prevent the resulting DNA damage. The Hopkins team says that in depleting the supply of oxygen radicals, the antioxidants may be destabilizing a tumor’s ability to grow under oxygen-starved conditions.
The investigators used mice implanted with either human lymphoma or human liver cancer cells. Both these cancers produce high levels of free radicals that can be suppressed by feeding the mice supplements of antioxidants, either vitamin C or N-acetylcysteine (NAC).
When the team examined cancer cells from mice not fed the antioxidants, they noticed 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,” says Ping Gao, Ph.D, lead author of the paper.
That finding led the researchers to suspect a protein known to be dependent on free radicals called HIF-1 (hypoxia-induced factor) was involved. They discovered that while this protein was abundant in untreated cancer cells taken from the mice, it disappeared in vitamin C-treated cells.
“When a cell lacks oxygen, HIF-1 helps it compensate,” explains study leader, Chi Dang, M.D., Ph.D., professor of medicine and oncology and Johns Hopkins family professor in oncology research. “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.”
Some rapidly growing tumors consume enough energy to easily suck out the available oxygen in their vicinity, making HIF-1 absolutely critical for their continued survival. HIF-1 can only operate, however, if it has a supply of free radicals. Since antioxidants remove these free radicals, HIF-1 does not work.
The authors 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 power.
The work is detailed this week in Cancer Cell.