Nearly 30 years after Nobel laureate Linus Pauling
famously and controversially suggested that
vitamin C supplements can prevent cancer, a team of Johns
Hopkins scientists has shown that in mice
at least, vitamin C — and potentially other
antioxidants — can indeed inhibit the growth of some
tumors, just not in the manner suggested by years of
The conventional wisdom of how antioxidants such as
vitamin C help prevent cancer growth is
that they grab up volatile oxygen free radical molecules
and prevent the damage they are known to do
to our delicate DNA. The Johns Hopkins study, led by Chi
Dang, professor of
and the Johns Hopkins Family Professor in Oncology
Research, unexpectedly found that the
antioxidants' actual role may be to destabilize a tumor's
ability to grow under oxygen-starved
conditions. The researchers' work is detailed in the
September issue of Cancer Cell.
"The potential anticancer benefits of antioxidants
have been the driving force for many clinical
and preclinical studies," Dang said. "By uncovering the
mechanism behind antioxidants, we are now
better suited to maximize their therapeutic use.
"Once again," he said, "this work demonstrates the
irreplaceable value of letting researchers
follow their scientific noses wherever it leads them."
The authors do caution that while vitamin C is still
essential for good health, this study is
preliminary and people should not rush out and buy bulk
supplies of antioxidants as a means of cancer
The Johns Hopkins investigators discovered the
surprise antioxidant mechanism while looking at
mice implanted with either human lymphoma (a blood cancer)
or human liver cancer cells. Both of 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, or
However, when the team examined cancer cells from
cancer-implanted 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," said Ping Gao, lead author of the
That conclusion led Gao and Dang to suspect that some
other mechanism was involved, such as a
protein known to be dependent on free radicals called HIF-1
(for hypoxia-induced factor), which was
discovered more than a decade ago by Johns Hopkins
researcher and co-author Gregg Semenza,
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,"
Dang said. "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. But HIF-1 can only operate
if it has a supply of free radicals. Antioxidants remove
these free radicals and stop HIF-1, and the
tumor, in its tracks.
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 research was funded by the National Institutes of
Authors on the paper are Dean Felsher, of Stanford;
and Gao, Huafeng Zhang, Ramani Dinavahi,
Feng Li, Yan Xiang, Venu Raman, Zaver Bhujwalla, Linzhao
Cheng, Jonathan Pevsner, Linda Lee, Gregg
Semenza and Dang, all of Johns Hopkins.