Curing Colorectal Cancer with High Doses of Vitamin C?
High levels of vitamin C equivalent to what’s found in 300 oranges could hold the key to stopping aggressive, hard-to-treat colorectal cancer in its tracks, according to a new study.
Injections of vitamin C slowed the growth of KRAS mutant and BRAF mutant colorectal tumors in cultured cells and mice, according to study author Dr. Lewis Cantley, the director of the Sandra and Edward Meyer Cancer Center and a professor in oncology research at Weill Cornell Medicine in New York City. He said the research team was interested in the possibility that the mutants were vulnerable to dehydroascorbic acid (DHA), the oxidized form of vitamin C, because DHA can enter cells through a glucose transporter (GLUT) that is expressed at very high levels in KRAS and BRAF mutant colorectal tumors.
“We examined human colorectal cancer cell lines that had either KRAS mutations or BRAF mutations, and found that they died when exposed to DHA,” explained Dr. Cantley. “In contrast, DHA did not kill cells that had wild-type KRAS or BRAF.”
The study showed that only tumors with high levels of GLUT1 transporters and a high basal level of reactive oxygen production — which are characteristics of KRAS and BRAF mutant colorectal cancers — are likely to respond, noted Dr. Cantley, who said it’s unlikely that oral vitamin C would achieve levels of DHA in the serum needed for effective therapy.
Dr. Cantley compared the intravenous injections of high doses of vitamin C to the opening of the GLUT1 glucose transporter “gate” that allows the DHA “Trojan horse” to enter the tumor cells. “Once in the tumor cells, DHA enhances oxidative stress in cells that already have high background oxidative stress due to the mutant oncogenes to ultimately cause cell death,” he explained.
“The surprise is that vitamin C is killing tumors, not because it is an antioxidant, but because it is spontaneously converted to DHA in an oxygen environment and that this is killing cells by acting as an oxidant rather than antioxidant,” said Dr. Cantley.
Controversy has surrounded the use of high doses of vitamin C for treating cancers, but enough responses have been seen in intravenous vitamin C injection studies over the years to keep oncologists interested in this possibility, according to Dr. Cantley. “Our study provided a rationale for why this might be beneficial in some cancer patients,” he added. “It also provided a mechanistic rationale for exploring the therapeutic use of vitamin C to treat colorectal cancers that carry KRAS or BRAF mutations.”
The study was published in the journal Science.
—Dan Cook
Reference:
1. Yun J, Mullarky E, Lu C, et al. Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH. Science. 2015 Nov 5. [Epub ahead of print]
