A drug approved by the FDA for the treatment of alcoholism appears to have the potential to fight malignant pleural mesothelioma, an aggressive form of lung cancer that is often unresponsive to conventional therapies.
Disulfiram (sold under the brand name Antabuse) blocks the processing of alcohol in the body by inhibiting acetaldehyde dehydrogenase. Some studies have suggested that the drug’s ability to bind to copper, a mineral often elevated in the blood serum of cancer patients, may also give it anti-tumor properties and the ability to make cancer cells more susceptible to chemotherapy.
In the new mesothelioma study, a team led by cancer researchers at Detroit’s Wayne State University School of Medicine administered copper complexed disulfiram (DSF-Cu) to mice with human mesothelioma, as well as to human mesothelioma cells in the lab. At a daily level of 50 mg/kg of body weight, DSF-Cu injections inhibited the growth of malignant pleural mesothelioma tumors in the mice and triggered cell-destroying apoptosis in the test tube.
In a summary of the new findings, lead author Vino Cheriyan, PhD, reports, “Gene-array based analyses revealed that DSF-Cu suppressed cell growth and metastasis-promoting genes…” DSF-Cu appeared to inhibit mesothelioma cell growth and survival by upregulating certain cell cycle inhibitors and by acting on the glycoprotein podoplanin, which is associated with metastasis and poor prognosis in mesothelioma. “Together with our in vivo studies, [this] underscores its potential as an anti-malignant pleural mesothelioma agent,” concludes Dr. Cheriyan in the online open-access medical journal PLoS One.
Disulfiram was discovered in the 1920s. In addition to supporting the treatment of chronic alcoholism, it has been studied as a treatment for several types of cancer, cocaine dependence, and HIV infection.
Pleural mesothelioma is a virulent cancer that starts on the membrane (pleura) surrounding the lungs. While the asbestos-induced cancer is very rare, it’s high mortality rate has made it the subject of intense cancer research around the world. About 2,500 people are diagnosed with mesothelioma in the US each year. In most cases, patients were inadvertently exposed to asbestos in an unsafe work environmental.
Source: Cheriyan, VT, “Disulfiram suppresses growth of the malignant pleural mesothelioma cells in part by inducing apoptosis”, April 1, 2014, PLoS One