The Effect of Different Glucose Concentrations on the Antiproliferative Activity of Metformin in MCF-7 Breast Cancer Cells.

The glucose-lowering drug metformin has been reported to have anticancer properties through unknown mechanisms. Other unknown factors that may influence its anticancer potential include the glycemic status of the patient. Therefore, the objective of this study is to determine the effect of different glucose environments on the antiproliferative potency and the cellular mechanism of action of metformin. Human breast cancer cells, MCF-7, were incubated in low, normal, elevated, and high glucose environments and treated with metformin. The antiproliferative potential of metformin and its effect on protein expression as well as its ability to induce cellular apoptosis and autophagy under different glucose environments, were determined using different molecular techniques. Metformin significantly inhibited cellular proliferation in a time- and glucose-concentration-dependent manner. In comparison to elevated glucose, low normal glucose alone induced a significant level of autophagy that was further increased in the presence of metformin. While glucose concentration did not appear to have an effect on the antiproliferative potency of metformin, the cellular basis of action was shown to be glucose-dependent. The antiproliferative mechanism of action of metformin in elevated and low normal glucose environments is mTOR-dependent, whereas, in the high glucose environment, the antiproliferative mechanism is independent of mTOR. This is the first study to report that both the antiproliferative potency and the cellular mechanism of action aredependent on the concentration of glucose.

The antiproliferative potential and mechanism of action of metformin in MCF-7 cells.

Aim: The current study aimed to investigate the potential antiproliferative activity of metformin, the effective concentration range, and the mechanism of action. Materials & methods: Human breast cancer cells, MCF-7 were treated with a serial dilution of metformin (10-150 µM) for 24 and 48 h. Potential antiproliferative activity of metformin and its ability in inducing cellular apoptosis and autophagy were also investigated. Results: Metformin inhibited MCF-7 proliferation in a concentration and time dependent manner, with 80 µM as the most effective concentration. Compared with nontreated cells, metformin induced significant levels of autophagy and apoptosis, which were confirmed by the reduction of mTOR and BCL-2 protein expression. Conclusion: The study confirms the antiproliferative activity of metformin, which may likely occur through AMPK signaling pathway.

The antidiabetic drug, metformin is tested in this work for its possible ability to inhibit the growth of breast cancer cells. Using different concentrations of the drug over different time points, the results showed that the drug was able to inhibit cancer growth through different mechanisms. The results also showed that the drug inhibits cancer growth by stimulating program cell death (apoptosis), as well as autophagy, where the cell breaks old and abnormal cellular substances.

Human exposure to aerosol from indoor gas stove cooking and the resulting nervous system responses.

Our knowledge of the effects of exposure to indoor ultrafine particles (sub-100 nm, #/cm3 ) on human brain activity is very limited. The effects of cooking ultrafine particles (UFP) on healthy adults were assessed using an electroencephalograph (EEGs) for brain response. Peak ultrafine particle concentrations were approximately 3 × 105 particle/cm3, and the average level was 1.64 × 105 particle/cm3 . The average particle number emission rate (S) and the average number decay rate (a+k) for chicken frying in brain experiments were calculated to be 2.82 × 1012 (SD = 1.83 × 1012 , R2  = 0.91, p = 0.0013) particles/min, 0.47 (SD = 0.30, R2  = 0.90, p < 0.0001) min-1 , respectively. EEGs were recorded before and during cooking (14 min) and 30 min after the cooking sessions. The brain fast-wave band (beta) decreased during exposure, similar to people with neurodegenerative diseases. It subsequently increased to its pre-exposure condition for 70% of the study participants after 30 min. The brain slow-wave band to fast-wave band ratio (theta/beta ratio) increased during and after exposure, similar to observed behavior in early-stage Alzheimer's disease (AD) patients. The brain then tended to return to its normal condition within 30 min following the exposure. This study suggests that chronically exposed people to high concentrations of cooking aerosol might progress toward AD.

The impact on heart rate and blood pressure following exposure to ultrafine particles from cooking using an electric stove.

Cooking is a major source of indoor particulate matter (PM), especially ultrafine particles (UFPs). Long-term exposure to fine and ultrafine particles (UFPs) has been associated with adverse human health effects. Toxicological studies have demonstrated that exposure to PM2.5 (particles with aerodynamic diameter smaller than 2.5 µm) may result in increased blood pressure (BP). Some clinical studies have shown that acute exposure to PM2.5 causes changes in systolic (SBP) and diastolic blood pressure (DBP), depending on the source of particles. Studies assessing the effect of exposure to cooking PM on BP and heart rate (HR) using electric or gas stoves are not well represented in the literature. The aim of this investigation was to perform controlled studies to quantify the exposure of 50 healthy volunteer participants to fine and ultrafine particles emitted from a low-emissions recipe for frying ground beef on an electric stove. The BP and heart rate (HR) of the volunteers were monitored during exposure and after the exposure (2 h post-exposure). Maximum UFP and PM2.5 concentrations were 6.5 × 104 particles/cm3 and 0.017 mg/m3, respectively. Exposure to UFPs from frying was associated with statistically significant increases in the SBP. The lack of food and drink during the 2 h post-cooking period was also associated with a statistically significant reduction in SBP. No statistically significant changes in DBP were observed. Physiological factors, including heat stress over the stove, movements and anxiety, could be responsible for an elevation in HR at the early stages of the experiments with a subsequent drop in HR after 90 min post-cooking, when study participants were relaxed in a living room.

The impact of frying aerosol on human brain activity.

Knowledge on the impact of the exposure to indoor ultrafine particles (UFPs) on the human brain is restricted. Twelve non-atopic, non-smoking, and healthy adults (10 female and 7 male, in average 22 years old) were monitored for brain physiological responses via electroencephalographs (EEGs) during cooking. Frying ground beef meat in sunflower oil using electric stove without ventilation was conducted. UFPs, particulate matter (PM) (PM1, PM2.5, PM4, PM10), CO2, indoor temperature, RH, oil and meat temperatures were monitored continuously throughout the experiments. The UFP peak concentration was recorded to be approximately 2.0 × 105 particles/cm3. EEGs were recorded before exposure, at end of cooking when PM peak concentrations were observed, and 30 min after the end of the cooking session (post-exposure). Brain electrical activity statistically significantly changed during post-exposure compared to the before exposure, suggesting the translocation of UFPs to the brain, occurring solely in the frontal and temporal lobes of the brain. Study participants older than 25 were more susceptible to UFPs compared to those younger than 25. Also, the brain abnormality was mainly driven by male rather than female study participants. The brain slow-wave band (delta) decreased while the fast-wave band (Beta3) increased similar to the pattern found in the literature for the exposure to smoking fumes and diesel exhaust.