Vitamin C can help stop the growth of cancerous tumors - just not how most scientists thought. In a significant finding, researchers led by Chi V. Dang of the Hopkins School of Medicine have uncovered a novel pathway by which antioxidants (for example, vitamin C) may limit tumor growth.
The report, published in Cancer Cell last week, challenges current thinking on how antioxidants act to suppress uncontrolled cell division. Nonetheless the study's results bolster previous data that support the use of antioxidants as cancer-combating drugs.
Antioxidants are broadly defined as molecules that prevent or slow the oxidation of other molecules. Oxidation occurs when a molecule loses electrons to another substance. What results is a molecule with one or more unpaired electrons and is termed a free radical.
Unpaired electrons are taboo in the biological world, so free radicals, longing for a mate for their lonely electrons, are known to be highly reactive. In this sense and as their name implies, free radicals are rather mercurial.
On the one hand they play important roles in many critical biological processes, such as cell signaling and the immune response. Nitric oxide, for example, is well-known as a key biological messenger.
On the other hand, one free radical stealing an electron from another, stable molecule often leads to a chain reaction of unchecked electron-stealing.
In some cases, DNA can be the victim of electron theft, especially when the free radicals involved are oxygen-based (members of a subclass called reactive oxygen species). In this case genetic material can be?quickly and irreversibly?degraded.
Adverse genetic mutations often increase and proliferate, interfering with the cycle of cell replication and, more often than not, producing a tumor or mass.
Though knowledge of antioxidants' anti-tumor properties has been well established since the 1970s, no study has ever conclusively shown the mechanism by which any one of them acts. Until recently, the protective effects of antioxidants were generally thought to arise from their ability to lower free radical reactivity, thus minimizing damage to genes and stabilizing the genome.
The Hopkins group's findings, however, appear to contradict the conventional wisdom. They recorded no difference between the genomes of vitamin C-treated and untreated mice that had been implanted with cancerous human cells. Instead of directly stabilizing the genome, antioxidants appear to fight tumor growth by curtailing a molecule called hypoxia-inducible factor 1 (HIF-1).
Under normal conditions, HIF-1 stimulates cells whose oxygen supplies are low to construct new oxygen-bringing blood vessels and to convert sugars into energy without using oxygen. When oxygen levels return to normal, HIF-1 is usually chemically tagged and targeted for degradation in the proteasome, the cell's garbage disposal.
Cancerous tumors, however, quickly gobble up the oxygen supplies of their constituent cells and thus need to maintain high HIF-1 levels. Predictably what drives HIF-1 activity are free radicals, all too plentiful in cancerous tumors. By disarming free radicals, antioxidants effectively stop tumor growth.
Moreover the researchers found that this process is dependent upon the activation by antioxidants of two enzymes, prolyl hydroxylase (PHD) and von Hippel-Lindau protein (VHL). Despite their frightening names, these enzymes are essentially biological middlemen, tagging HIF-1 for destruction but not doing any of the grunt work. That's left to the proteasome, as mentioned before.
Extending this discovery in mice to understand human cancer will likely prove challenging, but it provides a concrete basis for investigating and developing long-term, high-dose antioxidant therapies. In the meantime, keep drinking orange juice.
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