Current Evidence of the Role of the Myokine Irisin in Cancer

Regular exercise/physical activity is beneficial for the health of an individual and lowers the risk of getting different diseases, including cancer. How exactly exercise results in these health benefits is not known. Recent studies suggest that the molecule irisin released by muscles into the blood stream after exercise may be responsible for these effects. This review summarizes all the available in vitro/cell culture, animal and human studies that have investigated the relationship between cancer and irisin with the aim to shed light and understand the possible role of irisin in cancer. The majority of the in vitro studies indicate anticancer properties of irisin, but more animal and human studies are required to better understand the exact role of irisin in cancer.Brock Library Open Access Publishing Fun

Rosemary Extract as a Potential Anti-Hyperglycemic Agent: Current Evidence and Future Perspectives

Type 2 diabetes mellitus (T2DM), a disease on the rise and with huge economic burden to health care systems around the globe, results from defects in insulin action (termed insulin resistance) combined with impaired insulin secretion. Current methods of prevention and treatments for insulin resistance and T2DM are lacking in number and efficacy and, therefore, there is a need for new preventative measures and targeted therapies. In recent years, chemicals found in plants/herbs have attracted attention for their use as functional foods or nutraceuticals for preventing and treating insulin resistance and T2DM. Rosemary is an evergreen shrub indigenous to the Mediterranean region and South America, which contains various polyphenols. Rosemary extract and its polyphenolic constituents have been reported to have antioxidant, anti-inflammatory, anticancer, and anti-hyperglycemic properties. The current review summarizes the existing in vitro and in vivo studies examining the anti-diabetic effects of rosemary extract and its polyphenolic components and highlights the known mechanism of action

Resveratrol-fortification of red wine does not provide greater inhibition of human lung cancer cell survival compared to non-fortified wine.

Lung cancer is the leading cause of cancer-related deaths, and individuals with this disease often develop resistance to conventional cytotoxic therapies. Red wine and its polyphenolic component resveratrol, have been shown to have anticancer effects. Wines fortified with resveratrol have been marketed as having additional health benefits because of their increased polyphenolic content, however no studies exist examining this claim. The aim of the present study was to explore the effects of resveratrol-fortified red wine on lung cancer cell survival. Human NSCLC A549 cells were treated with varying concentrations of red wine with or without trans-resveratrol fortification. Cell survival was assessed using clonogenic assays and immunoblotting was used to explore the effects on Akt and ERK signaling molecules. Red wine significantly inhibited cell survival at concentrations as low as 0.02%, and significantly reduced phosphorylation of both Akt and ERK. No significant differences were seen between regular and resveratrol-fortified red wine. These data suggest that red wine may have considerable cancer preventive potential, however it does not support the use of resveratrol-fortified wine for additional health benefits.

Rosmarinic Acid, a Rosemary Extract Polyphenol, Increases Skeletal Muscle Cell Glucose Uptake and Activates AMPK

Skeletal muscle is a major insulin-target tissue and plays an important role in glucose homeostasis. Impaired insulin action in muscles leads to insulin resistance and type 2 diabetes mellitus. 5′ AMP-activated kinase (AMPK) is an energy sensor, its activation increases glucose uptake in skeletal muscle and AMPK activators have been viewed as a targeted approach in combating insulin resistance. We previously reported AMPK activation and increased muscle glucose uptake by rosemary extract (RE). In the present study, we examined the effects and the mechanism of action of rosmarinic acid (RA), a major RE constituent, in L6 rat muscle cells. RA (5.0 μM) increased glucose uptake (186 ± 4.17% of control, p < 0.001) to levels comparable to maximum insulin (204 ± 10.73% of control, p < 0.001) and metformin (202 ± 14.37% of control, p < 0.001). Akt phosphorylation was not affected by RA, while AMPK phosphorylation was increased. The RAstimulated glucose uptake was inhibited by the AMPK inhibitor compound C and was not affected by wortmannin, an inhibitor of phosphoinositide 3-kinase (PI3K). The current study shows an effect of RA to increase muscle glucose uptake and AMPK phosphorylation. RA deserves further study as it shows potential to be used as an agent to regulate glucose homeostasis.Brock University Library Open Access Publishing Fun

Inhibition of human lung cancer cell proliferation and survival by wine

Compounds of plant origin and food components have attracted scientific attention for use as agents for cancer prevention and treatment. Wine contains polyphenols that were shown to have anti-cancer and other health benefits. The survival pathways of Akt and extracellular signal-regulated kinase (Erk), and the tumor suppressor p53 are key modulators of cancer cell growth and survival. In this study, we examined the effects of wine on proliferation and survival of human Non-small cell lung cancer (NSCLC) cells and its effects on signaling events.Compounds of plant origin and food components have attracted scientific attention for use as agents for cancer prevention and treatment. Wine contains polyphenols that were shown to have anti-cancer and other health benefits. The survival pathways of Akt and extracellular signal-regulated kinase (Erk), and the tumor suppressor p53 are key modulators of cancer cell growth and survival. In this study, we examined the effects of wine on proliferation and survival of human Non-small cell lung cancer (NSCLC) cells and its effects on signaling events

Antidiabetic Properties of Naringenin: A Citrus Fruit Polyphenol

Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by insulin resistance and hyperglycemia and is associated with personal health and global economic burdens. Current strategies/approaches of insulin resistance and T2DM prevention and treatment are lacking in efficacy resulting in the need for new preventative and targeted therapies. In recent years, epidemiological studies have suggested that diets rich in vegetables and fruits are associated with health benefits including protection against insulin resistance and T2DM. Naringenin, a citrus flavanone, has been reported to have antioxidant, anti-inflammatory, hepatoprotective, nephroprotective, immunomodulatory and antidiabetic properties. The current review summarizes the existing in vitro and in vivo animal studies examining the anti-diabetic effects of naringeninBrock University Library Open Access Publishing Fun

Role of the Myokine Irisin on Bone Homeostasis: Review of the Current Evidence

Bone is a highly dynamic tissue that is constantly adapting to micro-changes to facilitate movement. When the balance between bone building and resorption shifts more towards bone resorption, the result is reduced bone density and mineralization, as seen in osteoporosis or osteopenia. Current treatment strategies aimed to improve bone homeostasis and turnover are lacking in efficacy, resulting in the search for new preventative and nutraceutical treatment options. The myokine irisin, since its discovery in 2012, has been shown to play an important role in many tissues including muscle, adipose, and bone. Evidence indicate that irisin is associated with increased bone formation and decreased bone resorption, leading to reduced risk of osteoporosis in post-menopausal women. In addition, low serum irisin levels have been found in individuals with osteoporosis and osteopenia. Irisin targets key signaling proteins, promoting osteoblastogenesis and reducing osteoclastogenesis. The present review summarizes the existing evidence regarding the effects of irisin on bone homeostasis.Brock Library Open Access Publishing Fun

Resveratrol enhances prostate cancer cell response to ionizing radiation. Modulation of the AMPK, Akt and mTOR pathways

<p>Abstract</p> <p>Background</p> <p>Prostate cancer (PrCa) displays resistance to radiotherapy (RT) and requires radiotherapy dose escalation which is associated with greater toxicity. This highlights a need to develop radiation sensitizers to improve the efficacy of RT in PrCa. Ionizing radiation (IR) stimulates pathways of IR-resistance and survival mediated by the protein kinase Akt but it also activates the metabolic energy sensor and tumor suppressor AMP-Activated Protein Kinase (AMPK). Here, we examined the effects of the polyphenol resveratrol (RSV) on the IR-induced inhibition of cell survival, modulation of cell cycle and molecular responses in PrCa cells.</p> <p>Methods</p> <p>Androgen-insensitive (PC3), sensitive (22RV1) PrCa and PNT1A normal prostate epithelial cells were treated with RSV alone (2.5-10 μM) or in combination with IR (2-8 Gy). Clonogenic assays, cell cycle analysis, microscopy and immunoblotting were performed to assess survival, cell cycle progression and molecular responses.</p> <p>Results</p> <p>RSV (2.5-5 μM) inhibited clonogenic survival of PC3 and 22RV1 cells but not of normal prostate PNT1A cells. RSV specifically sensitized PrCa cells to IR, induced cell cycle arrest at G1-S phase and enhanced IR-induced nuclear aberrations and apoptosis. RSV enhanced IR-induced expression of DNA damage (γH2Ax) and apoptosis (cleaved-caspase 3) markers as well as of the cell cycle regulators p53, p21^cip1and p27^kip1. RSV enhanced IR-activation of ATM and AMPK but inhibited basal and IR-induced phosphorylation of Akt.</p> <p>Conclusions</p> <p>Our results suggest that RSV arrests cell cycle, promotes apoptosis and sensitizes PrCa cells to IR likely through a desirable dual action to activate the ATM-AMPK-p53-p21^cip1/p27^kip1and inhibit the Akt signalling pathways.</p

Regulation of metabolic effects in L6 muscle cells by sulfonylureas and the protein tyrosine phosphatase inhibitors vanadate and pervanadate

grantor: University of TorontoNon-insulin-dependent or Type II diabetes mellitus (NIDDM) is a disease characterized by insulin deficiency and insulin resistance. Treatment is directed at improving either one or both of these abnormalities. The most commonly used pharmacological agents to treat NIDDM are the sulfonylurea drugs. A controversial and unanswered question about sulfonylureas is whether they possess any direct actions on peripheral insulin target tissues. The effects of gliclazide and glyburide on glucose uptake in L6 skeletal muscle cells, a model of a major insulin target tissue, were investigated. These studies demonstrate that gliclazide and glyburide similarly increase glucose transport into L6 cells which is associated with an increase in total cellular and plasma membrane GLUT1 glucose transporter levels. The mechanism appears to involve stabilization of GLUT1 at the plasma membrane. Since many patients with NIDDM do not respond to currently available oral hypoglycemic agents, a great deal of research into understanding insulin action and resistance and the development of novel agents is ongoing. Vanadium compounds ape protein tyrosine phosphatase inhibitors which have been useful probes to study insulin signalling and have also been proposed as potential therapeutic agents. The effects of the vanadium compounds sodium orthovanadate and pervanadate on glucose and amino acid transport and their mechanism of action were investigated. The results demonstrate that vanadate and pervanadate mimic insulin to stimulate glucose transport in L6 cells but inhibit amino acid (MeAIB) transport by the insulin-sensitive system A transporter. The data suggest that this inhibition may be mediated by inhibition of a protein tyrosine phosphatase. It was also found that the stimulation of glucose transport by vanadate and pervanadate is mediated by a signaling pathway that differs from that of insulin and importantly is independent of PI 3-kinase, the enzyme involved in the insulin signalling of glucose transport. These findings contribute new knowledge to our understanding of the effects and mechanisms of action of the oral hypoglycemic sulfonylurea drugs and vanadium compounds. Taken together the results support the continued use of sulfonylureas and the potential use of vanadium compounds in disease associated with insulin resistance.Ph.D