The team studied colorectal cancer (CRC) and honed in on the specific cancer cells that bore KRAS or BRAF mutations. In these cells, the team made two prior observations that led them to their current study. First, they noted that the KRAS- and BRAF-mutated cells expressed a very high level of a protein called GLUT1, a transporter protein. GLUT1 functions to transport glucose and dehydroascorbic acid (DHA), the oxidized form of vitamin C, across the plasma membrane and into the cell. Secondly, they noted that the cell then spent nearly all of its available antioxidants to soak up the free radicals produced when DHA was converted back to vitamin C. Because of excess GLUT1 protein and DHA, the cells eventually died from oxidative stress.
Putting two and two together, the team exploited this vulnerability in KRAS- and BRAF-mutated cells to systematically overload it with vitamin C, hoping the cells would succumb to oxidative stress and die. Indeed, they observed that large doses of vitamin C did kill KRAS- and BRAF-mutated CRC cells in culture. They then moved to a mouse model of CRC, specifically caused by the KRAS/BRAF mutations. With daily high dose injections of vitamin C, the team observed the smaller and fewer colon tumors in treated vs. untreated mice.“We were surprised that KRAS- and BRAF-mutant cancer cells could take up DHA at such a high rate that the DHA consumed all the cells’ antioxidants, which are needed for cancer cell survival. Most cancer cells—and normal cells—do not have enough glucose transporters to allow DHA to enter at such a rapid rate.” - Dr. Lewis Cantley, senior author of the study.
Though using vitamin C to fight cancer is not a wholly new idea, the results are highly promising, as it identified a subset of colorectal cancer with a specific mutational background that responds to vitamin C. Furthermore, the team identified the biological pathway involved in this response, legitimizing the responses they observed.
With this information, Dr. Cantley hopes to design clinical trials to test whether CRC patients with KRAS- and BRAF-mutations are more likely to respond positively to vitamin C treatments. If vitamin C could curb the growth of colon cancer in the human clinical trials as it did in mice, then they will have not only identified a potent treatment, but they will have also identified a group of people for whom the drug will benefit the most. The ramifications could also extend to other types of KRAS/BRAF-driven cancers that may benefit from vitamin C treatments. Pancreatic cancer, for example, is one that’s commonly lethal and associated with KRAS mutations.
Promising as the results are, there is one caveat to know before we all overload on orange juice and vitamin C supplements. The effects of tumor shrinkage in mice were achieved with extremely high daily doses of vitamin C injections – the equivalent of one person consuming 300 oranges a day, a near impossibility. In addition, Dr. Cantley also noted that “even if vitamin C ultimately shows good results in humans with this or the BRAF mutation, it is likely that we will need to combine it with other agents that enhance the formation of reactive oxygen species in the tumor to achieve tumor shrinkage.”
It probably doesn’t hurt, though, to add some fresh oranges to your daily diet! Watch the video to learn more about vitamin C!
Additional Sources: Science Mag