AACR (KC) 01-Oct-08
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Vitamin C Supplements may Reduce Benefit from Wide Range of Anticancer Drugs
PHILADELPHIA - In pre-clinical studies, vitamin C appears to substantially reduce the effectiveness of anticancer drugs, say researchers at Memorial Sloan-Kettering Cancer Center.
These new findings, published in the October 1 issue of Cancer Research, a publication of the American Association of Cancer Research (AACR), came from studying laboratory cancer cells and mice, but the study's authors say the same mechanism may affect patient outcomes, although they add this premise needs to be tested.
"The use of vitamin C supplements could have the potential to reduce the ability of patients to respond to therapy," said Heaney, an Associate Attending Physician at Memorial Sloan-Kettering Cancer Center.
Use of vitamin C during cancer treatment has been controversial. Some studies have suggested that because vitamin C is an antioxidant it might be beneficial to cancer patients. But some classes of chemotherapy drugs produce "oxygen free radicals," unpaired oxygen molecules that can fatally react with other molecules in a cell, forcing cell death. In this theory, vitamin C could sop up the radicals, keeping the cancer cell alive despite chemotherapy treatment.
Heaney and his colleagues tested a wide variety of chemotherapy drugs - those that produce reactive oxygen and those that work in other ways - on cancer cells in the laboratory, that were pretreated with dehydroascorbic acid (DHA), the form that ascorbic acid (vitamin C) takes to enter cells.
They found to their surprise that every chemotherapy drug they tested - which included targeted agents like Gleevec - did not work as well if cells were pretreated with vitamin C, as they did on untreated cancer cells. In the cell culture experiments, 30 to 70 percent less cancer cells treated with vitamin C were killed depending on the drug tested.
They then checked these findings by implanting the cancer cells into mice, and again found that, in an animal model system, while chemotherapy kept untreated cancer in check, tumors grew more rapidly in mice that were given cancer pretreated with vitamin C.
The research team, which includes researchers from Columbia University, then delved into the mechanism by which vitamin C may be protecting these cells, and discovered that it wasn't because the nutrient was neutralizing oxygen-free radicals.
They found instead that DHA was restoring viability to the cancer cell's damaged mitochondria - the cell's all-important power plant that, when injured, sends signals to force a cell to die.
"Vitamin C appears to protect the mitochondria from extensive damage, thus saving the cell," Heaney said. "And whether directly or not, all anticancer drugs work to disrupt the mitochondria to push cell death."
Heaney says that the amount of DHA used in the experiments resulted in an intracellular buildup similar to what could be seen in cancer patients using large supplemental doses of vitamin C.
Researchers at Memorial Sloan-Kettering Cancer Center have long been researching the connection between vitamin C and cancer therapy, and these new findings expand on their earlier observation that vitamin C seems to accumulate within cancer cells more than in normal cells.
"We recognized that DHA is the form of vitamin C that gets into cells, and that the tumor microenvironment allows cancer cells to convert more vitamin C into DHA," he said. "Inside the cell, DHA is converted back into ascorbic acid, and it gets trapped there and so is available to safeguard the cell."
Heaney says that he suspects that vitamin C is good for the cells of normal tissue because it provides more protection for the mitochondria, and thus probably extends cell life. "But that isn't what you want when you are trying to eliminate cancer cells," said Heaney, who notes that cancer patients should eat a healthy diet, which includes foods rich in vitamin C. It is use of large doses of over-the-counter vitamin C that is worrisome, he says.
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