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- Date:
- January 9, 2017
- Source:
- University of Iowa Health Care
- Summary:
- Cancer researchers have homed in on how high-dose
vitamin C kills cancer cells. Vitamin C breaks down to generate hydrogen
peroxide, which can damage tissue and DNA. The new study shows that
tumor cells with low levels of catalase enzyme activity are much less
capable of removing hydrogen peroxide than normal cells, and are
more susceptible to damage and death when they are exposed to high doses
of vitamin C.
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FULL STORY
Vitamin C has a patchy history as a cancer
therapy, but researchers at the University of Iowa believe that is
because it has often been used in a way that guarantees failure.
Most vitamin C therapies involve taking the substance orally.
However, the UI scientists have shown that giving vitamin C
intravenously -- and bypassing normal gut metabolism and excretion
pathways -- creates blood levels that are 100 -- 500 times higher than
levels seen with oral ingestion. It is this super-high concentration in
the blood that is crucial to vitamin C's ability to attack cancer cells.
Earlier work by UI redox biology expert Garry Buettner found that at
these extremely high levels (in the millimolar range), vitamin C
selectively kills cancer cells but not normal cells in the test tube and
in mice. Physicians at UI Hospitals and Clinics are now testing the
approach in clinical trials for pancreatic cancer and lung cancer that
combine high-dose, intravenous vitamin C with standard chemotherapy or
radiation. Earlier phase 1 trials indicated this treatment is safe and
well-tolerated and hinted that the therapy improves patient outcomes.
The current, larger trials aim to determine if the treatment improves
survival.
In a new study, published recently in the December issue of the journal
Redox Biology,
Buettner and his colleagues have homed in on the biological details of
how high-dose vitamin C (also known as ascorbate) kills cancer cells.
The study shows that vitamin C breaks down easily, generating
hydrogen peroxide, a so-called reactive oxygen species that can damage
tissue and DNA. The study also shows that tumor cells are much less
capable of removing the damaging hydrogen peroxide than normal cells.
"In this paper we demonstrate that cancer cells are much less
efficient in removing hydrogen peroxide than normal cells. Thus, cancer
cells are much more prone to damage and death from a high amount of
hydrogen peroxide," says Buettner, a professor of radiation oncology and
a member of Holden Comprehensive Cancer Center at the University of
Iowa. "This explains how the very, very high levels of vitamin C used in
our clinical trials do not affect normal tissue, but can be damaging to
tumor tissue."
Normal cells have several ways to remove hydrogen peroxide, keeping
it at very low levels so it does not cause damage. The new study shows
that an enzyme called catalase is the central route for removing
hydrogen peroxide generated by decomposing vitamin C. The researchers
discovered that cells with lower amounts of catalase activity were more
susceptible to damage and death when they were exposed to high amounts
of vitamin C.
Buettner says this fundamental information might help determine which
cancers and which therapies could be improved by inclusion of high-dose
ascorbate in the treatment.
"Our results suggest that cancers with low levels of catalase are
likely to be the most responsive to high-dose vitamin C therapy, whereas
cancers with relatively high levels of catalase may be the least
responsive," he explains.
A future goal of the research is to develop methods to measure catalase levels in tumors
