PMID: 

Int Immunopharmacol. 2019 Jun ;71:277-284. Epub 2019 Mar 28. PMID: 30927738

Abstract Title: 

Isoflavone daidzein regulates immune responses in the B6C3F1 and non-obese diabetic (NOD) mice.

Abstract: 

Daidzein (DAZ), a dominant isoflavone in various natural products such as soybeans, has been gaining attention due to the beneficial health effects (e.g., protection against cancer and diabetes) of its metabolites. Our major hypothesis was that dietary exposure to the soy phytoestrogen DAZ could modulate the immune responses toward a protective effect and lead to improved metabolic functions (such as glucose metabolism). In this study, we applied complementary mouse models, the hybrid B6C3F1 and inbred type 1 diabetes prone non-obese diabetic (NOD) mice, to investigate if DAZ exposure modulated the immune responses. The animals were orally administered DAZ at various physiological doses (2-20 mg/kg body weight) during adulthood. DAZ significantly altered the relative organ weights in female B6C3F1 mice and decreased the B cell population (represented by CD3IgM), while the T cell populations (represented by CD3IgM, CD4CD8and CD4CD8) were increased. In addition, DAZ dosing produced a decrease in the percentage of late apoptotic thymocytes. However, the activities cytotoxic T cells and natural killer cells were not altered in the B6C3F1 mice. In NOD mice, the blood glucose level and glucose tolerance were not affected by DAZ exposure, but DAZ modulated the antibody production, as shown by increased levels of IgGin NOD females and IgGin NOD males. Further, DAZ increased CD8CD25splenocytes in NOD females. Taken together, DAZ induced an immunomodulatory effect in both NOD and B6C3F1 mouse strains; however, minimal effects on glucose homeostasis were observed.

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PMID: 

Life Sci. 2020 Mar 15 ;245:117387. Epub 2020 Jan 30. PMID: 32007575

Abstract Title: 

Synergetic inhibition of daidzein and regular exercise on breast cancer in bearing-4T1 mice by regulating NK cells and apoptosis pathway.

Abstract: 

The aim of this study was to investigate the inhibition of daidzein or/and regular exercise on breast cancer and to reveal the potential biological mechanisms. BALB/c mice pretreated with regular exercise training for 20 days (15 m/min, 60 min/d) were orthotopically transplanted with mouse breast cancer cells (4T1), and then treated with daidzein (145 mg/kg) by gavage for another 22 days. Results showed that exercise or daidzein inhibited tumor growth in mice to a different degree. Particularly, co-treatment with exercise and daidzein showed an obviously synergistic inhibition on the tumor growth (P 

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PMID: 

Front Physiol. 2019 ;10:1602. Epub 2020 Jan 24. PMID: 32038286

Abstract Title: 

Effect of Acute and Chronic Aerobic Exercise on Immunological Markers: A Systematic Review.

Abstract: 

The effects of aerobic exercise on the immune system are not yet fully defined in the scientific literature. This fact demonstrates the need to investigate its influence on existing immunological markers by classifying and quantifying their acute and chronic effects.To investigate the effects of acute and chronic aerobic exercise on inflammatory markers of healthy adults.This study is a systematic review according to PRISMA recommendations. The following databases were searched: MEDLINE (via PubMed), Science Direct, Scopus, Web of Science, SciELO, Bireme and Cochrane Library, and article references. The last search was performed in March 2019. We included randomized controlled trials (RCTs) and non-randomized controlled trials (NRCTs) investigating the acute and chronic effects of aerobic exercise on immune markers in healthy male and female adults aged 20 to 45 years, without restrictions in language or year of publication. Two authors independently analyzed the studies by reading the titles, abstracts, and full texts. Risk of Study bias was analyzed using Cochrane's Risk of Bias Tool.We included 15 studies in this systematic review, 13 of which were acute intervention and 2 were chronic, with 296 participants, 196 men and 100 women all being healthy individuals. It was observed that the acute intervention promotes changes in most immunological markers, while the chronic intervention interferes with a smaller proportion, this being in lymphocyte subpopulations. In the evaluation of quality, it was found that most studies did not present a high risk of bias in the evaluated aspects, but an unclear related risk of bias was observed, requiring a more careful analysis.Thus, it can be concluded that the evidence indicates that acute and chronic interventions may modify most immune markers, but aspects such as gender, contraceptive pill use in women, physical capacity of the investigated individuals, environment, and type and intensity of the exercises may interfere with these markers as well as the data analysis. Therefore, this review suggests that further research is needed to contribute to the confirmation and estimation of results.

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PMID: 

Aging (Milano). 1997 Feb-Apr;9(1-2):42-56. PMID: 9177585

Abstract Title: 

Exercise, immunity and aging.

Abstract: 

In general population, many protective immune responses are impaired in old age, leading to an increased risk of infection. However, recent studies in SENIEUR subjects (healthy centenarians who are examples of successful aging) suggest that complex remodeling and reshaping of the immune system occurs with aging. An appropriate regular regimen of endurance exercise might help elderly to lead a quality of life by preserving immune function. However, very little is known regarding the interaction between exercise, aging and the immune system. Given that a number of age-related changes occur in many physiological systems which are known to alter the immune function both at rest and during exercise, it would be of value to learn the extent to which both acute and chronic exercise influence immune function in the elderly. The immune system response to exercise is multifaceted, depending on the nature of exercise. Significant interaction between the neuroendocrine and immune systems, and the role of lifestyle factors in immune function are known to occur. In theory, moderate exercise should help to reverse the adverse effects of aging upon the immune system by increasing the production of endocrine hormones which may contribute to less accumulation of autoreactive immune cells by enhancing the programmed cell death. Active elderly subjects demonstrated a significantly greater proliferative response to phytohemagglutinins (PHA) and to pokeweed mitogen (PWM), and higher rates of interleukin-2 (IL-2), interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) production. A moderate training program can enhance the resting natural killer (NK) cell function of healthy elderly people, potentially increasing resistance to both viral infections and preventing the formation of malignant cells. Recent studies have suggested that endurance training in later life is associated with a lesser age-related decline in certain aspects of circulating T cell function and related cytokine production. It is important that the dose of physical activity needed to optimize immune function be defined more clearly at various points during the aging process both in females and males in order to optimize the immune function and to prevent any rise in adverse effects of exercise on the elderly population.

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PMID: 

J Appl Physiol (1985). 2004 Feb ;96(2):450-4. PMID: 14715676

Abstract Title: 

Exercise alters the IGF axis in vivo and increases p53 protein in prostate tumor cells in vitro.

Abstract: 

Epidemiological studies report that regular physical activity can reduce the risk for prostate cancer, the most common solid-tumor cancer in US men. Regular exercise alters the serum IGF axis in vivo and reduces cell proliferation while increasing apoptosis in serum-stimulated LNCaP prostate cancer cells in vitro. The present study tests the hypothesis that these effects on tumor cell lines are mediated by enhancement of the function of the p53 gene known to arrest cell growth and induce apoptosis. When LNCaP cells were cultured in exercise serum and compared with control serum, cell growth was reduced by 27%, and there was a similar 33% decrease in proliferating cell nuclear antigen protein, a marker for cell cycling. Apoptosis was increased by 371% with the exercise serum, and there was a 100% increase in p53 protein (75.2 +/- 2.0 vs. 38.2 +/- 2.0 pg/microg protein). When serum was used to stimulate LN-56 cells, a cell line with nonfunctional p53 derived from LNCaP, no significant reduction in cell growth or increase in apoptosis with the exercise serum was observed. These results indicate that exercise training alters serum factors in vivo that increase cellular p53 protein content and is associated with reduced growth and induced apoptosis in LNCaP prostate cancer cells in vitro.

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PMID: 

Nat Rev Immunol. 2019 09 ;19(9):563-572. PMID: 31175337

Abstract Title: 

Can physical activity ameliorate immunosenescence and thereby reduce age-related multi-morbidity?

Abstract: 

Remodelling of the immune system with age – immunosenescence – is a substantial contributor to poor health in older adults, with increasing risk of infections, cancer and chronic inflammatory disease contributing to age-related multi-morbidity. What is seldom considered when examining the immune response of an aged individual is that the immune system is profoundly influenced by physical activity. Habitual physical activity levels decline with age, with significant consequences for muscle mass and function. Skeletal muscle is a major immune regulatory organ and generates a range of proteins, termed myokines, which have anti-inflammatory and immunoprotective effects. Several studies indicate that maintaining physical activity has immune benefits in older adults, for example, it reduces the systemic inflammation associated with chronic age-related diseases. Here, we discuss how physical activity can prevent or ameliorate age-related multi-morbidity by boosting immune function, and we consider whether physical activity could improve immunotherapy outcomes in age-related conditions such as cancer.

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PMID: 

Am J Physiol Endocrinol Metab. 2011 Sep ;301(3):E504-10. Epub 2011 Jun 7. PMID: 21653222

Abstract Title: 

Exercise-induced muscle-derived cytokines inhibit mammary cancer cell growth.

Abstract: 

Regular physical activity protects against the development of breast and colon cancer, since it reduces the risk of developing these by 25-30%. During exercise, humoral factors are released from the working muscles for endocrinal signaling to other organs. We hypothesized that these myokines mediate some of the inhibitory effects of exercise on mammary cancer cell proliferation. Serum and muscles were collected from mice after an exercise bout. Incubation with exercise-conditioned serum inhibited MCF-7 cell proliferation by 52% and increased caspase activity by 54%. A similar increase in caspase activity was found after incubation of MCF-7 cells with conditioned media from electrically stimulated myotubes. PCR array analysis (CAPM-0838E; SABiosciences) revealed that seven genes were upregulated in the muscles after exercise, and of these oncostatin M (OSM) proved to inhibit MCF-7 proliferation by 42%, increase caspase activity by 46%, and induce apoptosis. Blocking OSM signaling with anti-OSM antibodies reduced the induction of caspase activity by 51%. To verify that OSM was a myokine, we showed that it was significantly upregulated in serum and in three muscles, tibialis cranialis, gastronemius, and soleus, after an exercise bout. In contrast, OSM expression remained unchanged in subcutaneous and visceral adipose tissue, liver, and spleen (mononuclear cells). We conclude that postexercise serum inhibits mammary cancer cell proliferation and induces apoptosis of these cells. We suggest that one or more myokines secreted from working muscles may be mediating this effect and that OSM is a possible candidate. These findings emphasize that role of physical activity in cancer treatment, showing a direct link between exercise-induced humoral factors and decreased tumor cell growth.

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PMID: 

J Urol. 2001 Sep ;166(3):1185-9. PMID: 11490320

Abstract Title: 

Evidence of an inhibitory effect of diet and exercise on prostate cancer cell growth.

Abstract: 

PURPOSE: A high fat diet and sedentary lifestyle may predispose men to prostate cancer through effects on serum factors such as hormones. We evaluated the effects of a low fat, high fiber diet and exercise intervention on serum stimulated growth of established prostate cancer cell lines.MATERIALS AND METHODS: Fasting serum was obtained from 13 overweight men before and after undergoing an 11-day low fat, high fiber diet and exercise intervention. Serum was also obtained from 8 men who had complied with the regimen for a mean of 14.2 years. Hormone dependent LNCaP and independent PC-3 prostate cancer cell lines were grown in culture medium containing 10% of subject pre-intervention or post-intervention serum and viable cells were counted after 48 hours. Anthropometry, serum free testosterone, lipids and glucose were measured in all subjects.RESULTS: Post-intervention serum from each of the 11-day intervention subjects reduced LNCaP cell growth by a mean of 30% compared with pre-intervention serum from each (p

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PMID: 

PLoS One. 2013 ;8(7):e67579. Epub 2013 Jul 5. PMID: 23861774

Abstract Title: 

Effect of acute exercise on prostate cancer cell growth.

Abstract: 

Physical activity is associated with reduced risk of several cancers, including aggressive prostate cancer. The mechanisms mediating the effects are not yet understood; among the candidates are modifications of endogenous hormone levels. Long-term exercise is known to reduce serum levels of growth stimulating hormones. In contrast, the endocrine effects of acute endurance exercise include increased levels of mitogenic factors such as GH and IGF-1. It can be speculated that the elevation of serum growth factors may be detrimental to prostate cancer progression into malignancy. The incentive of the current study is to evaluate the effect of acute exercise serum on prostate cancer cell growth. We designed an exercise intervention where 10 male individuals performed 60 minutes of bicycle exercise at increasing intensity. Serum samples were obtained before (rest serum) and after completed exercise (exercise serum). The established prostate cancer cell line LNCaP was exposed to exercise or rest serum. Exercise serum from 9 out of 10 individuals had a growth inhibitory effect on LNCaP cells. Incubation with pooled exercise serum resulted in a 31% inhibition of LNCaP growth and pre-incubation before subcutaneous injection into SCID mice caused a delay in tumor formation. Serum analyses indicated two possible candidates for the effect; increased levels of IGFBP-1 and reduced levels of EGF. In conclusion, despite the fear of possible detrimental effects of acute exercise serum on tumor cell growth, we show that even the short-term effects seem to add to the overall beneficial influence of exercise on neoplasia.

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PMID: 

Exerc Immunol Rev. 2020 ;26:80-99. PMID: 32139350

Abstract Title: 

Mobilizing serum factors and immune cells through exercise to counteract age-related changes in cancer risk.

Abstract: 

An increasing body of evidence suggests that age-related immune changes and chronic inflammation contribute to cancer development. Recognizing that exercise has protective effects against cancer, promotes immune function, and beneficially modulates inflammation with ageing, this review outlines the current evidence indicating an emerging role for exercise immunology in preventing and treating cancer in older adults. A specific focus is on data suggesting that muscle- derived cytokines (myokines) mediate anti-cancer effects through promoting immunosurveillance against tumourigenesis or inhibiting cancer cell viability. Previous studies suggested that the exercise-induced release of myokines and other endocrine factors into the blood increases the capacity of blood serum to inhibit cancer cell growth in vitro. However, little is known about whether this effect is influenced by ageing. Prostate cancer is the second most common cancer in men. We therefore examined the effects of serum collected before and after exercise from healthy young and older men on the metabolic activity of androgen-responsive LNCaP and androgen-unresponsive PC3 prostate cancer cells. Exercise-conditioned serum collected from the young group did not alter cell metabolic activity, whereas post-exercise serum (compared with pre-exercise serum) from the older men inhibited the metabolic activity of LNCaP cancer cells. Serum levels of candidate cancer-inhibitory myokines oncostatin M and osteonectin increased in both age groups following exercise. Serum testosterone increased only in the younger men postexercise, potentially attenuating inhibitory effects of myokines on the LNCaP cell viability. The data from our study and the evidence in this review suggest that mobilizing serum factors and immune cells may be a key mechanism of how exercise counteracts cancer in the older population.

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