Physical exercise as a synchronizer of circadian rhythms in cancer

Abstract

The cancer is among the leading causes of morbidity and mortality worldwide. The causes for the formation of this tumor may be by a genetic determinant, however, the lifestyle appear to be the primary contributor to it. Behavioral, metabolic and physiological daily oscillations are driven by an endogenous circadian clock. This endogenous circadian clock can often suffer external influences, environmental. In modern society, changes in lifestyle lead to a frequent disruption of the endogenous circadian homeostasis, providing an increase in risk for various diseases, including cancer. Studies demonstrate that the abnormal cell proliferation, which is characteristic of tumor cells is intimately related to the circadian rhythm and regulation of cellular metabolism. Despite the evidence of changes in the circadian rhythm and tumorigenesis, the molecular mechanisms underlying this effect remain poorly understood. Physical exercise can alter circadian rhythms and taking into account that physical exercise affects all tissues and body systems, interacting in an immuno psychoneuroimmunoendocrine modulation system and the changes in the balance of that system during chronic diseases, such as cancer, promote a misrepresentation of the circadian rhythm. A regular program of exercise can be a useful intervention and low cost as a strategy to improve the quality of life of patients and survivors of cancer. Therefore, our goal is to assess whether the mechanisms involved in tumor growth inhibition by physical training can be correlated with the chronomarker role of physical exercise. Also, determine if the gene markers of circadian rhythm in the tumor and peripheral tissues can be modulated by hours of physical training. The lineage mice will be used background C57BL / 6J mice (WT) and the animals will be divided into 3 groups: control group; tumor group; tumor + exercise group. There will be a subdivision of groups and amines will train in three different periods: 8 am, 8 pm and train group at varying times during the week (8 am on Monday - 12 pm on Tuesday - 4 pm on Wednesday - 8 pm on Thursday - 00 am on Friday). The animals will be submitted to aerobic training after a week of tumor inoculation. They will be held two weeks of training comprising 5 training sessions per week of 40 to 60 minutes, in which the animals will run to a speed corresponding to 60% of the maximum speed. To analyze the circadian changes, the animals will be euthanized every 4 hours a day (8 am, 12 pm, 4 pm, 8 pm, 00 am e 4 am). In skeletal muscle, adipose tissue, liver and tumor tissue will carry out gene expression of clock genes factors involved in the oxidative metabolism of inflammatory factors and cell cycle and protein expression of inflammatory cytokines.