In a study detailed this week in the journal Cancer Cell, researchers from Johns Hopkins University investigated the mechanisms that took effect after they implanted human cancer cells into mice and fed the mice the antioxidants vitamin C or N-acetylcysteine. Uncovering a mechanism behind antioxidants could result in more condition-specific and therapeutic uses for the ingredients. The potential cancer-protective benefits of antioxidants, such as vitamin C, have been documented in numerous clinical studies in the past. The established understanding as to how antioxidants can aid in the prevention of cancer growth is that they absorb free radicals and prevent the damage these molecules can do to DNA structure. The researchers implanted the mice with either human lymphoma or human liver cancer cells because both forms produce high levels of free radicals that can be suppressed by feeding mice antioxidant supplements. The team was alerted to a new possible mechanism of antioxidant functioning when it examined cancer cells from those cancer-implanted mice that were not fed antioxidants. There was an absence of any significant DNA damage in these mice. This led the authors to suspect some other mechanism was involved, such as a protein known to be dependent on free radicals called HIF-1 (hypoxia-induced factor), "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," said Ping Gao, John Hopkins researcher and lead author of the study paper. The team found that while HIF-1 was abundant in untreated cancer cells taken from the mice, it had disappeared from those cells treated with vitamin C that were taken from similar animals. "When a cell lacks oxygen, HIF-1 helps it compensate," said Dr Chi Dang, professor of medicine and oncology at Johns Hopkins. "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." Antioxidants can block the supply of free radicals that is essential to HIF-1's survival, according to the researchers. And, because, HIF-1 plays a role in keeping tumors alive, the antioxidant thereby indirectly takes away the life force of these tumors. The Johns Hopkins researchers backed-up their findings on HIF-1's role in tumour growth by creating cancer cells with a genetic variant of the protein that did not require free radicals to be stable. In these cells, antioxidants no longer had any cancer-fighting power. They underscored that the study is preliminary and consumers should not yet take antioxidants as a means of cancer prevention. Source: Goa, Ping et al. "HIF-Dependent Antitumorigenic Effect of Antioxidants In Vivo." Cancer Cell. 2007 Sep;12(3):230-8.