Vitamin C protects against tumors in rodent model of breast cancer


In the July, 2009 issue of the journal Carcinogenesis, researchers at Columbia University report the discovery of a protective property for vitamin C against estrogen-induced breast tumors in an estrogen-dependent breast tumor-sensitive strain of rats.

In their introduction to the article, the authors remark that estrogens can stimulate cancer through estrogen receptor dependent and independent mechanisms. The estrogen receptor-independent pathway of estrogen-induced breast cancer involves the activation of the body's estrogens by cytochrome P450 enzymes to generate catechol estrogens that can have adverse effects on DNA when undergoing oxidative metabolism. The current study was designed to determine whether reducing the metabolism of estrogen to catechol estrogens with the estrogen metabolic inhibitor alpha-napthoflavone (ANF) and lowering oxidative stress with the antioxidant vitamin C would reduce the development of estrogen-induced tumors.

The researchers divided the animals to receive a control substance, the estrogen 17-beta-estradiol (E2), vitamin C (added to drinking water), alpha-napthoflavone, 17-beta-estradiol plus vitamin C, or 17-beta-estradiol plus alpha-napthoflavone. Each of these groups was divided to receive treatment for 7, 15, 120 or 240 days.

At the end of each treatment period, the animals were examined for tumor incidence, and mammary and liver tissue levels of the oxidative stress marker 8-iso-Prostane F-2-alpha and the antioxidants superoxide dismutase, catalase, and glutathione peroxidase.

While no mammary tumors were found in the groups that did not receive estradiol, 82 percent of the rats that received estradiol alone developed mammary tumors after 240 days. In animals that received estradiol and vitamin C for 240 days, mammary tumor incidence was reduced to 29 percent. Tumors appeared later in those that received vitamin C and were mostly encapsulated, as opposed to the invasive tumors found in the estradiol only group.

Treatment with alpha-napthoflavone completely prevented tumors in rats that received estradiol. Alpha-napthoflavone and vitamin C were also found to lower oxidative stress in estradiol-treated animals. While SOD and glutathione peroxidase increased in animals exposed to estradiol alone, they remained unchanged compared to controls in animals that received estradiol with ANF and vitamin C, which suggests that the increased oxidative stress experienced by the rats that received estradiol alone resulted in enhancement of these antioxidant enzymes.

"The present study is the first to demonstrate the inhibition of breast carcinogenesis by antioxidant vitamin C or the estrogen metabolic inhibitor ANF in an animal model of estrogen-induced carcinogenesis," the authors announced. "These results suggest that E2 metabolism and oxidant stress are critically involved in estrogen-induced breast carcinogenesis.