Will MAO inhibitors help with prostate cancer?
"Old" antidepressants may be a new way to treat prostate cancer
Anna Stavina, XX2 century
Prostate cancer, like other oncological diseases, is able to spread through the body or metastasize. Its peculiarity is that almost all patients with malignant prostate tumors have metastases in the bone tissue, which, in turn, leads to multiple fractures and a sharp decrease in the quality of life of patients. In a new study, scientists have discovered an enzyme that helps prostate cancer cells form metastases in bone tissue. Moreover, it turned out that some types of antidepressants are able to block this enzyme.
The results of the work carried out by Jason Wu from Washington State University Spokane were published in the publication Cancer Cell (MAOA-Dependent Activation of Shh-IL6-RANKL Signaling Network Promotes Prostate Cancer Metastasis by Engaging Tumor-Stromal Cell Interactions).
Prostate cancer is the second most common cancer among men living in the United States. It is second only to skin cancer. In Russia, the statistics look somewhat different: lung cancer is in the first place, it is Russian men who suffer from it most often. And malignant prostate diseases, according to various data, are only the second or third (after skin cancer) in frequency.
According to the American Cancer Society, about 161330 new cases of prostate cancer will be registered in the United States in 2017. More than 26 thousand men will die from this disease, and approximately 90% of the deceased will have metastatic bone damage.
In a new study, Wu and his colleagues found that the enzyme monoamine oxidase A (MAO-A) is involved in the signaling cascade, which simplifies the process of penetration of prostate cancer cells into bone tissue. Scientists came to this conclusion by injecting human cancer cells into mice and analyzing the activity of MAO-A. It turned out that this enzyme stimulates the activity of three other proteins, which, in turn, activate the work of osteoclasts, cells that destroy bone tissue. This is necessary for bone renewal – simultaneously with the destruction of bone tissue in the body, its synthesis takes place, and normally the speed of these two processes in the adult body coincides.
"Cancer cells can stimulate osteoclasts in a specific way," says Wu. "The phenomenon we observed was explained by the fact that the rate of destruction of existing bone tissue was much faster than the rate of creation of a new one."
When the researchers reduced the production of MAO-A in cancer cells, their ability to spread in bone tissue also decreased. Conversely, when enzyme synthesis was activated, the number of metastases in mice increased.
In the next part of the work, the scientists used the irreversible selective MAO inhibitor clorgiline (clorgiline). Once this drug was used as an antidepressant. It turned out that the effect of clorgilin prevents MAO-A from activating proteins that stimulate the work of osteoclasts. Thus, the use of an MAO inhibitor reduced the ability of cancer cells to spread through bone tissue and grow in it.
"Our observations explain why "old" antidepressants may be useful for patients with late–stage prostate cancer suffering from symptoms of metastasis," Wu stressed.
The researchers also noted that in clinical practice, drugs are currently used that are similar in mechanism of action to clorgiline. Currently, a group of scientists is studying the effects of these drugs on tumor growth.
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16.03.2017