Disulfiram against cancer
A remedy for alcoholism can help in the treatment of cancer
Polina Gershberg, Naked Science
Creating an effective anti-cancer therapy remains one of the most difficult tasks in medical research. The fact is that cancer cells use the host's own immune system to grow and spread, which eventually becomes deadly. Immune cells such as macrophages, which normally protect normal cells of the body, are captured by malignant cells and turn into MAO cells (macrophages associated with a tumor). Such macrophages inhabit the tumor microenvironment and suppress the antitumor immune response, providing more active proliferation of cancer cells.
In recent years, MAO has attracted a lot of attention from scientists as a potential target for anti-cancer therapy. A group of researchers from the University of Tokyo led by Professor Yuya Terashima has shown that by blocking a certain protein in macrophages associated with a tumor, it is possible to suppress the development of tumors. And disulfiram, a drug used in the treatment of alcoholism, can act as an inhibitor.
Fourteen years ago, under the leadership of Terashima, the cytoplasmic protein FROUNT was discovered, which regulates the movement of macrophages in the body. This protein plays an important role in chemotaxis of cells – reactions to chemical stimuli. When the expression of FROUNT is blocked, cells (including macrophages) practically lose their ability to respond to chemokines, substances that control cell migration.
In a new study published in Nature Communications (Terashima et al., Targeting FROUNT with disulfiram suppresses macrophage accumulation and its tumor-promoting properties), scientists screened 131,200 compounds to find an effective inhibitor of FROUNT. They, as we have already written above, turned out to be disulfiram. This drug is now used as a drug for alcoholism: it stops the process of decomposition of ethyl alcohol in the body at the acetaldehyde stage. Alcohol consumption while taking disulfiram causes intoxication, accompanied by nausea, vomiting and malaise, and forms an aversion to the taste and smell of ethanol.
It turned out that disulfiram is also able to bind to the FROUNT molecule, making it inaccessible for interaction with the components of chemokine signaling. When tested on mice, disulfiram inhibited the movement of macrophages and thereby made it easier for other cells of the immune system to fight against the tumor.
In the future, scientists want to understand more deeply the interaction of disulfiram with signaling proteins that affect cell movement, since macrophages are a problem in various types of diseases. The work of researchers from the University of Tokyo can become the basis for the creation of drugs – inhibitors of the broad-spectrum protein FROUNT.
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