Disulfiram (Antabuse) is a drug given to alcoholics to prevent them from drinking, but for decades doctors have noticed the medication appears to have an unexpected side effect: fighting cancer. Now, new research from the Karolinska Institute in Sweden has revealed the biological mechanism behind Antabuse's effect on cancer.
The study, published earlier this week in Nature, is the culmination of years of research and the combined efforts of scientists from five countries. In the paper, the team explains how Antabuse appears to “freeze” tumor growth by inhibiting an important protein.
Antabuse is an odorless and nearly tasteless powder that, when consumed, causes an unpleasant physical reaction with alcohol, ranging from sweating and hyperventilation to nausea and vomiting. The drug works by interfering with the body's ability to metabolize or break down alcohol. Specifically, the drug disables aldehyde dehydrogenase, an enzyme in the liver that breaks down alcohol, allowing the body to process it. If aldehyde dehydrogenase is unable to function, alcohol builds up in the bloodstream and causes physical problems.
However, as shown in this new study, Antabuse has another effect on the body. For their study, the researchers observed the drug's effect on both living mice and on human cancer cells. In doing so, they noted that when the drug is metabolized it causes the protein, NPL4, to clump together with the enzyme p97, immobilizing the protein. This “freezes” the cancer cells and prevents them from disposing of unnecessary proteins. The build-up stresses the cancer cells and eventually causes them to die, Science Mag reported.
Results were even more pronounced when the drug was combined with copper, and the drug did not discriminate when it came to what type of cancer cells it killed. In the study it was just as helpful in killing prostate, breast and colon cancer. In addition, only cancer cells are affected by Antabuse while normal cells seem to be unharmed. The reason for this is unclear.
The connection between the drug and cancer treatment dates back decades, with the first case report acknowledging the connection published in 1977 in Progress in Clinical and Biological Research. The case detailed a breast cancer patient who also was an alcoholic. She was given Antabuse to treat her alcoholism, but an autopsy upon her death (which was due to falling from a window, not cancer) revealed that her body was clinically cancer-free despite having no further cancer treatment. In fact, the only drug she had continued to use was Antabuse.
The new study is the first to suggest a biological explanation for this side effect of the drug.
The new study now is the first to suggest a biological explanation for this side effect. Still, Dr. Matthew Galsky, an oncologist and a professor of medicine at the Icahn School of Medicine at Mount Sinai, told Newsweek that it may be too soon to count this as a cancer cure just yet.
“Obviously the major questions are, that’s great that it works in test tubes, but what does this mean for patients, and how do we test that?”
Galsky noted that the study was extremely detailed and showed exactly how this drug affects cancer cells, but we still do not know if the doses used to achieve these results in the laboratory can be safe and effective in human patients.
"Unfortunately, we want advances quick when we are treating cancer because this is a devastating disease, and repurposing drugs does shorten this time,” said Galsky. “Still, we need to do a careful investigation in the clinic to make sure that it’s safe to give adequate doses.”
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