Maybe Linus Pauling was on to something after all. Decades ago the Nobel Prize–winning chemist was relegated to the fringes of medicine after championing the idea that vitamin C could combat a host of illnesses, including cancer. Now, a study published online today in Science reports that vitamin C can kill tumor cells that carry a common cancer-causing mutation and—in mice—can curb the growth of tumors with the mutation. If the findings hold up in people, researchers may have found a way to treat a large swath of tumors that has lacked effective drugs. "This [could] be one answer to the question everybody's striving for," says molecular biologist Channing Der of the University of North Carolina, Chapel Hill, one of many researchers trying to target cancers with the mutation. The study is also gratifying for the handful of researchers pursuing vitamin C, or ascorbic acid, as a cancer drug. Maybe people will finally pay attention," says vitamin C researcher Mark Levine of the National Institute of Diabetes and Digestive and Kidney Diseases.
In 1971, Pauling began collaborating with a Scottish physician who had reported success treating cancer patients with vitamin C. But the failure of two clinical trials of vitamin C pills, conducted in the late 1970s and early 1980s at the Mayo Clinic in Rochester, Minnesota, dampened enthusiasm for Pauling’s idea. Studies by Levine’s group later suggested that the vitamin must be given intravenously to reach doses high enough to kill cancer cells. A few small trials in the past 5 years—for pancreatic and ovarian cancer—hinted that IV vitamin C treatment combined with chemotherapy can extend cancer survival. But doubters were not swayed. "The atmosphere was poisoned" by the earlier failures, Levine says. A few years ago, Jihye Yun, then a graduate student at Johns Hopkins University in Baltimore, Maryland, found that colon cancer cells whose growth is driven by mutations in the gene KRAS or a less commonly mutated gene, BRAF, make unusually large amounts of a protein that transports glucose across the cell membrane.
The transporter, GLUT1, supplies the cells with the high levels of glucose they need to survive. GLUT1 also transports the oxidized form of vitamin C, dehydroascorbic acid (DHA), into the cell, bad news for cancer cells, because Yun found that DHA can deplete a cell’s supply of a chemical that sops up free radicals. Because free radicals can harm a cell in various ways, the finding suggested “a vulnerability” if the cells were flooded with DHA, says Lewis Cantley at Weill Cornell Medicine in New York City, where Yun is now a postdoc. Cantley’s lab and collaborators found that large doses of vitamin C did indeed kill cultured colon cancer cells with BRAF or KRAS mutations by raising free radical levels, which in turn inactivate an enzyme needed to metabolize glucose, depriving the cells of energy. Then they gave daily high dose injections—equivalent to a person eating 300 oranges—to mice engineered to develop KRAS-driven colon tumors. The mice developed fewer and smaller colon tumors compared with control mice.
Cantley hopes to soon start clinical trials that will select cancer patients based on KRAS or BRAF mutations and possibly GLUT1 status. His group’s new study "tells you who should get the drug and who shouldn't," he says. Cancer geneticist Bert Vogelstein of Johns Hopkins University, in whose lab Yun noticed the GLUT1 connection, is excited about vitamin C therapy, not only as a possible treatment for KRAS-mutated colon tumors, which make up about 40% of all colon cancers, but also for pancreatic cancer, a typically lethal cancer driven by KRAS. “No KRAS-targeted therapeutics have emerged despite decades of effort and hundreds of millions of dollars [spent] by both industry and academia,” Vogelstein says. Others caution that the effects seen in mice may not hold up in humans. But because high dose vitamin C is already known to be safe, says cancer researcher Vuk Stambolic of the University of Toronto in Canada, oncologists “can quickly move forward in the clinic." One drawback is that patients will have to come into a clinic for vitamin C infusions, ideally every few days for months, because vitamin C seems to take that long to kill cancer cells, Levine notes.
But Cantley says it may be possible to make an oral formulation that reaches high doses in the blood—which may be one way to get companies interested in sponsoring trials.Findings from a new study offer further evidence of the cancer-fighting properties of vitamin C. This time, research shows the powerful antioxidant may be effective in combating a class of cancerous tumors – including colorectal cancer cells – that can be particularly difficult to treat by conventional means. Findings of the study, which showed the vitamin was effective in curbing cancer-causing mutations in mice, were published recently in the journal Science. Vitamin C is already known for its effectiveness in detoxifying the body and boosting the immune system. Notably championed by globally respected scientist Dr. Linus Pauling and other advocates as a treatment for cancer and heart disease, these latest findings on vitamin C may open the door for its use as treatment for some of the most challenging cancers.
It may sound incredible that a deadly disease like cancer could be treated by something as simple (and safe) as vitamin C. For decades, naysayers denied what Nobel Prize-winning chemist Pauling and others outside the conventional medical establishment had discovered: Vitamin C can be effective against many of the serious illnesses that have plagued mankind – including cancer. The most recently published study using cell culture and mice shows that vitamin C was effective at killing tumor cells that carry a common cancer-causing mutation. The hope is that the findings may eventually lead to the ability to use vitamin C to create a variety of targeted treatments against deadly cancers. In the study, researchers from Harvard Medical School, Weill Cornell Medicine, The Sidney Kimmel Comprehensive Cancer Center, Cold Spring Harbor Laboratory and Tufts Medical Center teamed up to investigate the effect of high doses of vitamin C on colorectal tumor formation. Using roughly the equivalent of the amount of vitamin C found in 300 oranges, the scientists were able to document impaired growth of KRAS-mutant and BRAF-mutant colorectal tumors in cultured cells as well as in mice.
Typically, the health benefits of vitamin C are associated in large part with its role as an effective antioxidant, helping to prevent or at least delay certain types of damage to cells. However, this latest study shows an entirely different role regarding its effect on certain forms of colorectal cancer, with it actually inducing oxidation in cancer cells. In oxygen-rich environments, like arteries, a portion of vitamin C is oxidized and transformed into a new compound known as dehydroascorbic acid or DHA. This new compound is able to act as a Trojan horse and pass through the cancer cell membrane, thanks to a protein glucose transmitter. Once inside, the cancer cell’s natural antioxidants attempt to convert DHA back to ascorbic acid, but are unable to keep up and instead become depleted, with the cancer cell then dying of oxidative stress. Because certain colorectal cancer cells produce greater amounts of reactive oxygen than other cell types, they need more antioxidants to survive.