MAO-A enzyme and prostate cancer
S.Kholin, Scientific.ru
Monoamine oxidase A (MAO-A) is an extremely important enzyme, without which many biochemical processes and physiological functions would be impossible. MAO-A is located in the mitochondria of cells; its biological role is associated with the cleavage of amine compounds, primarily endogenous neurotransmitters, hormones and biologically active substances (adrenaline, norepinephrine, dopamine, histamine, serotonin, melatonin, etc.), as well as exogenous amines entering the body with food and drugs.
Monoamine oxidase is present in almost all tissues of the body, however, the greatest activity of this enzyme was detected in the liver, the wall of the gastrointestinal tract, in various parts of the nervous system. A by-product of MAO-A activity is hydrogen peroxide, which stimulates the formation of reactive oxygen species and lipid peroxidation in cells. Normally, the intensity of these processes is low, and the resulting products are quickly neutralized by antioxidant enzymes. If the activity of MAO-A increases significantly, then the probability of damage to DNA molecules increases sharply, followed by the transformation of healthy cells into tumor cells. This is one of the leading mechanisms of the appearance of malignant neoplasms.
Recently, it has been suggested that there is a close relationship between the increased activity of MAO-A and the growth rate of some forms of prostate cancer in men.
This disease is considered extremely dangerous, since in the vast majority of cases it occurs and proceeds unnoticed for a long time for the patient; the appearance of the first subjective symptoms most often indicates a far-advanced stage of the process, when treatment practically does not give tangible results due to the formation of distant secondary tumors (metastases). The latter are formed mainly in the bone system and grow faster than the primary tumor. That is why prostate cancer in most countries of the world ranks third in the frequency of causes of death of men from malignant neoplasms, and the main method of its treatment continues to be total surgical removal of the affected prostate tumor [1,2].
A group of scientists from the USA and China, led by Jason Boyang Wu [3], conducted a complex study aimed at identifying the relationship between the intensity of prostate cancer growth and the activity of the MAO-A enzyme. For this purpose, the biochemical processes and structural and functional disorders associated with changes in the activity of MAO-A in samples of healthy tissue and human prostate tumors, as well as in cultures (individual lines) of cells of these neoplasms and their transplants in laboratory animals were analyzed in detail.
As a result of the study, it was found that with an increase in the activity of MAO-A, epithelial-mesenchymal transformation is stimulated, or, in other words, intensive "rejuvenation" (transition to an immature state) of prostate cells, with a simultaneous increase in the rate of formation of reactive oxygen species (ROS). This is followed by hypoxia (oxygen starvation) of cells, the regulation of their division is disrupted, which is why uncontrolled reproduction and growth of atypical cells with characteristic features of malignant neoplasm are observed. The cells of such tumors exhibit increased invasiveness (the desire to germinate into surrounding tissues), which is accompanied by intensive formation of metastases (including distant ones). The degree of increase in MAO-A activity in prostate cancer tissue clearly correlates with the severity of the course and outcome of the disease in patients. With pharmacological inhibition of MAO-A activity, the growth of prostate tumors is significantly reduced, and in some cases completely stops; at the same time, the appearance of metastases is not observed.
Thus, it is proved that an increase in the activity of the enzyme monoamine oxidase A contributes to the appearance of malignant prostate tumors with a high degree of invasiveness and a tendency to metastasis. The search for new drugs that inhibit the activity of MAO-A will significantly improve the prevention and treatment of this serious disease.
[1] Beer et al., Enzalutamide in Metastatic Prostate Cancer before Chemotherapy (N. Engl. J. Med., 2014)
[2] Bill-Axelson et al., Radical Prostatectomy or Watchful Waiting in Early Prostate Cancer (N. Engl. J. Med., 2014)
[3] Wu et al., Monoamine oxidase A mediates prostate tumorigenesis and cancer metastasis (J. Clin. Invest., 2014)
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