ИСТИНА

The main goal of most cancer treatment methods is to induce the death of tumor cells in order to free the patient's body from the tumor. Therefore, the identification of factors that return tumors the ability to apoptosis or necroptosis, will contribute both to the prevention of cancer and improve their treatment. One of these factors may be metabolic formaldehyde associated with an increased general metabolism of amino acids and nucleotides in a cancer cell. The accumulation of formaldehyde in cancer cells and the body of patients is accompanied by the activation of release processes from endogenous formaldehyde, followed by a change in the activity of the aldehyde dehydrogenase 1 and 2 (ALDH1 and ALDH2) genes involved in the oxidation of formaldehyde. It can be assumed that the suppression of oxidation of endogenous formaldehyde and its accumulation in the cell may contribute to the death of cancer cells. To test this assumption, we used a culture of Her2/neu-positive human breast cancer cells. We found that, when treating cancer cells with Her2/neu-specific monoclonal antibodies trastuzumab, cell death was accompanied by suppression of ALDH2 activity in cells and the accumulation of formaldehyde in them. This result was confirmed by us in experiments using disulfiram, an inhibitor of ALDH1 and ALDH2, a known agent widely used for the treatment of alcoholism. It turned out that, in the presence of disulfiram, firstly, the effect of trastuzumab on cancer cells sharply increased, and, secondly, it itself caused the death of cancer cells, accompanied by an increased production of formaldehyde cells. In the study of the mechanisms of manifestation of cell death, we found that the death of cancer cells caused by the action of formaldehyde is not apoptosis, but most likely a manifestation of necroptosis. This study was performed with financial support from the Russian Science Foundation (project No. 16-14-00002).