13 SEP 2007
Vindicated at last? Maybe vitamin C does cure cancer!
(?)
Those old enough to remember the first moon landing may also remember
the brilliant chemist Linus Pauling, quantum theorist, explorer of chemical
bonds, double-time Nobel Prize winner, anti-nuclear campaigner, and advocate
of vitamin C as a cure for many ills.
Including colds and cancer.
Pauling's scientific triumphs covered many fields, but his fervent advocacy of vitamin C aroused scorn and nearly scuttled his reputation.
Linus Pauling (1901-1994), was a pioneering scientist with broad interests and two Nobel prizes. When he began advocating the healing powers of vitamin C, he was denounced as a crank. But was Pauling on to something? Photo: NIH
Vitamin C is called an antioxidant because it can de-activate free radicals, which are atoms or groups of atoms that can damage molecules like DNA. If antioxidants can protect DNA, they would seem able to fight cancer and maybe prolong life.
But early enthusiasm over antioxidants has dimmed after long-term, large-scale and expensive studies failed to show much benefit, if any. And now comes a research group from Johns Hopkins Medical Institutions reporting that several antioxidants, including good-ol' vitamin C, actually do fight cancer in mice.
O say can you C?
But there's a strange twist to the story: Although the antioxidants are indeed destroying free radicals, they do not fight cancer by protecting DNA from damage.
The new report comes from a team directed by Chi Dang, a Johns Hopkins professor of medicine, cell biology and oncology. Dang had been looking at the role of free radicals and antioxidants in cancer, and he knew that antioxidants can inhibit some tumors.
But
even though the free radicals had contributed to the cancers, the expected
DNA damage was absent. That was suggestive, says Ping Gao, also of Johns Hopkins,
who was the new paper's lead author. "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."
Without vitamin C, your teeth would fall out due to scurvy. But could the antioxidant powers of vitamin C fight cancer? Graphic: Wikipedia
A matter of survival
To understand Dang's new view of antioxidants, we need to meet HIF-1 (hypoxia-induced
protein, if you must know). HIF is a "survival protein" that cells use
to stay alive when the oxygen level plummets, and it's particularly helpful
for fast-growing tumor cells, which deplete local oxygen stores as they
burn sugar to produce energy. "When a cell lacks oxygen, HIF-1 helps it
compensate," explains Dang, by allowing it to "convert sugar to energy
without using oxygen."
Most cells constantly make both HIF and an enzyme that degrades it. But when the oxygen level is low and free radicals are present, the degrading enzyme fails, so the HIF level rises.
Thus free radicals promote cellular survival in the low-oxygen zone. This is normal and normally good -- except when a cancer cell is getting the survival benefit.
Photo: USDA
C what you see
So Dang confronted a paradox - free radicals cause cancer, but they don't always start the process by damaging DNA. Antioxidants fight both free radicals and cancer, but how does that work if the free radicals did not affect the DNA in the first place?
Then Dang learned that vitamin C could help degrade HIF. Could that explain the inhibition of cancer?
To find out, Dang, Gao and colleagues implanted two types of human cancers into mice, then fed some of the animals the antioxidants vitamin C and N-acetylcysteine. The tumors shrank only in the mice that got the antioxidant.
The experiments showed that the antioxidants were indeed jump-starting the destruction of the survival protein HIF, forcing the tumors to stop growing.
If antioxidants fight cancer indirectly by reactivating the enzyme that destroys HIF, it's helpful that most common cancers show some degree of oxygen shortage, and thus may need HIF for survival.
Vitamin
C and another antioxidants helped mice defeat lymphoma, seen here as whitish,
irregular tumor mass cells on the left side of this liver. Photo:
NIH
On trial: C you in court?
If further animal research confirms the new-found relationship among HIF,
antioxidants and cancer, Dang wants to start human trials. Anyone who
has followed cancer prevention may question the wisdom of yet another
antioxidant trial. After all, at least one large trial found
more cancer among the people who took antioxidants.
But instead of dosing large numbers of healthy people, as done previously,
Dang would try to prevent cancer from reappearing just after surgery.
"Even if most of the tumor is taken out through surgery, there is often
a recurrence," he says. "Now that we understand at least one 
mechanism
by which antioxidants work, that leaves the door open to a well thought-out
study to see if antioxidants could prevent recurrence."
Although Dang is excited to see vitamin C attacking cancer, he is not promoting mega-dose vitamin C therapy. And in that respect, he parts company with Linus Pauling, the brilliant chemist whose theories and textbooks were bedrocks of chemistry during the 20th century, but whose claims for vitamin C have lain in disrepute for so long.
And how would Pauling react to evidence for his radical claim that vitamin C fights cancer? "I think if he is looking down, he has at least a smirk," says Dang. "He was probably right, but through a mechanism that was not recognized at the time."
- David Tenenbaum
Related Why Files
• Diet
and Blindness
• Tangled Brain
• Antioxidants and Love
• Free Radicals and Aging
Bibliography
• HIF-Dependent Antitumorigenic Effect
of Antioxidants In Vivo, Gao et al, Cancer Cell, Sept., 2007.
• Report that vitamin C degrades HIF
