NEW YORK, N.Y., February 28, 1997 -- Laboratory research by Memorial Sloan-Kettering Cancer Center scientists shows that HIV-infected immune cells take in more vitamin C and glucose than their healthy counterparts, which may aid replication of the AIDS virus. At the same time, however, extremely high levels of the vitamin are more toxic to the HIV-infected cells than to healthy immune cells, the investigators report in the Feb. 28 issue of the Journal of Biological Chemistry.
³HIV-infected cells grown in the laboratory appear to be more sensitive to the toxic effects of vitamin C,² explained Dr. David W. Golde, Physician-in-Chief of Memorial Hospital and senior author of the paper. ³At the same levels of exposure, the HIV-infected cells took in more vitamin C than uninfected immune cells.²
The laboratory research provides the foundation to begin to understand the relationship among vitamin C, HIV infection, and cell metabolism, and may lead to new therapeutic targets to counter the AIDS virus, he added. Vitamin C is essential to the human body and is necessary for normal function of the immune system.
The researchers studied vitamin C uptake and its effects on AIDS-virus production in HIV-infected and healthy immune cells, after finding in previous studies that cancer cells also take in more glucose and vitamin C than normal cells. In addition, Dr. Golde and his colleagues were the first to prove, in 1993, that the same molecule that allows glucose into cells also serves as a route for vitamin C to enter. Although vitamin C is used by cells in one chemical form (ascorbic acid), it enters cells in another form (dehydroascorbic acid). Once inside the cell, this vital nutrient is reconverted to its original form, whose different shape and size prevent it from leaving the cell.
This series of studies prompted Dr. Golde and his colleagues to ask whether HIV-infected cells also take in higher-than-normal levels of glucose and vitamin C. In the new study, led by Dr. Coralia Rivas and Dr. Juan Carlos Vera of Memorial Sloan-Kettering¹s Molecular Pharmacology and Therapeutics Program, the researchers studied the effects of vitamin C in four HIV-infected cell lines and four identical, but uninfected, immune cell lines. They found that compared with the healthy cells, the HIV-infected cells:
- have greater numbers of specialized cell-surface receptors through which glucose and vitamin C enter;
- experience a three- to five-fold increase in the uptake of vitamin C in the form of dehydroascorbic acid; and
- accumulate two to three times more vitamin C in the form of ascorbic acid.
³We noticed that shortly after infection with HIV, the cells put out more glucose-transport molecules on their surfaces, which allow more vitamin C to enter,² Dr. Golde said. ³HIV-infected cells seem to want more glucose and vitamin C. But if they take in too much vitamin C, they die.²
When the researchers exposed both HIV-infected and healthy immune cells to varying levels of vitamin C, they observed a range of effects. At levels of vitamin C comparable to those normally found in the body, the nutrient either had no effect or caused a slight increase in viral replication. But exposure to high vitamin C levels ‹ more than 20 times greater than normal ‹ decreased replication of the AIDS virus and was generally more toxic to HIV-infected cells than to the uninfected cells.
Such high blood levels of vitamin C can¹t be achieved by taking it orally because most supplemental vitamin C is excreted in the urine, Dr. Golde said. He and his colleagues are planning follow-up studies of vitamin C¹s effects in patients infected with the AIDS virus.
Memorial Sloan-Kettering Cancer Center is the world¹s oldest and largest private institution devoted to prevention, patient care, research, and education in cancer. Throughout its long, distinguished history, the Center has played a leadership role in defining the standard of care for patients with cancer. In 1996, Memorial Sloan-Kettering was named the nation¹s best cancer center for the fourth consecutive year by U.S. News & World Report.