Supplementary vitamin C might hinder cancer chemotherapy

NEW YORK (Reuters Health) - Vitamin C supplements taken during chemotherapy might substantially reduce the benefits of that therapy, according to a recent group of in vitro and animal studies of cancer cells.

Although foreshadowed by earlier research, US investigators also noted an unexpected finding: Vitamin C provided cancer cells with significant protection against a variety of antineoplastic agents, including both those that generate reactive oxygen species and those that do not. (The researchers had originally theorized that vitamin C would blunt the cytotoxic effects of only the former.) As a result, the study suggested a common mechanism behind the cytotoxic effects of many chemotherapeutic agents.

As to whether normal dietary intake of vitamin C is potentially problematic for cancer patients, "there are no data to suggest that there is any advantage to vitamin C deficiency during chemotherapy," cautioned lead author Dr. Mark L. Heaney, Memorial Sloan-Kettering Cancer Center, New York, in an interview with Reuters. "It is in fact possible that vitamin C deficiency could detrimentally affect overall health."

The researchers dosed a leukemia cell line and a lymphoma cell line with five widely used antineoplastic drugs: vincristine, doxorubicin, methotrexate, cisplatin and imatinib mesylate. Half of the cells had been pretreated with dehydroascorbic acid (DHA), the commonly transported form of vitamin C, they report in the October 1st issue of Cancer Research.

The DHA reduced the cytotoxicity of all five agents, regardless of their mechanism of action, by 30% to 70%. In addition, a dose-dependent effect was seen; cytotoxicity was reduced more in cells that had higher concentrations of vitamin C.

The same lymphoma cell line was used to induce tumors in mice, which were then treated with DHA, doxorubicin or both. Those given DHA alone did not experience increased tumor growth, but at day 32 of the study, mice that received DHA 2 hours before receiving doxorubicin had tumors about four times larger than did mice treated with doxorubicin alone (p = 0.01).

The study also showed that the DHA pretreatment did not alter the tumor cells' uptake of doxorubicin, suggesting that vitamin C interferes with cancer chemotherapy inside the cell.

Another part of the study found that all of the chemotherapeutic agents tested led to a rapid reduction in mitochondrial membrane potential, and that pretreatment with DHA prevented early chemotherapy-induced mitochondrial membrane depolarization by all five agents. The researchers concluded that "mitochondrial membrane depolarization may be a common mechanism that contributes to the cytotoxicity of many chemotherapeutic agents, including highly selective agents, such as imatinib."

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