Navigation Links
Study: Metformin for breast cancer less effective at higher glucose concentrations
Date:10/24/2013

A University of Colorado Cancer Center study published online this month in the journal Cell Cycle shows that breast cancer cell growth, motility and aggression is promoted by excess glucose, as experienced by patients with diabetes and metabolic syndrome. The study also showed that patients with high glucose may require higher doses of the drug metformin to achieve the same anti-cancer activity as patients with normal glucose levels.

Metformin, the most common first-line drug in the treatment of type-2 diabetes, has been shown in previous studies to reduce breast cancer risk, improve survival, and increase the effectiveness of chemotherapy. Numerous Phase III clinical trials are currently evaluating the benefits and best uses of metformin in breast cancer patients.

"We show that metformin works differently in high- compared to low-glucose conditions. Not only does it require a higher concentration of metformin to be active in high-glucose conditions, but we report that the drug regulates different genes within cancer cells at high as compared to normal glucose levels," says Ann Thor, MD, CU Cancer Center investigator, Todd Professor of Pathology at the University of Colorado School of Medicine, and the study's principal investigator.

The study evaluated the effects of metformin on 17 breast cancer cell lines representing each of the molecular subtypes of the disease, at varying glucose levels.

"Commonly, lab studies of metformin are performed with very high glucose concentrations about 17 millimols of glucose per liter. But the average glucose level in healthy humans is only about one third of that dose about 5 millimols per liter. And individuals with diabetes may have glucose at 10 millimols per liter. We wanted to study metformin activity under these conditions," Thor says.

So the question was this: how would metformin perform in breast cancer cells grown at more realistic, human levels of glucose?

"Results show that when you drop glucose down to human levels, metformin has an even bigger effect at standard doses. When glucose is high you need more metformin to achieve the same results," Thor says.

Thor also points out that skeptics of metformin treatment for cancer in general or breast cancer in particular frequently point to the high concentrations of metformin needed to create results in the laboratory.

"Our data helps to explain why higher doses of metformin are required to obtain anti-cancer effects when cancer cells are grown in the lab, as compared to its use in humans," Thor says.

Interestingly, "it wasn't simply that the metformin effectiveness went up as glucose came down, but that entirely new mechanisms of action were present at lower glucose levels," Thor says.

Specifically, Thor and colleagues used RNA expression arrays to discover which genes were affected by metformin at high and low glucose concentrations. At high glucose concentrations, metformin primarily affected genes involved in metabolic processes and cell proliferation; at low glucose concentrations, metformin affected genes controlling cellular process and programmed cell death.

In addition to affecting the growth of breast cancer cells, Thor and colleagues show the drug decreases the ability of breast cancer cells to move within the body a task necessary for the spread of the disease to other sites.

"An extension of this data implies that in breast cancer patients with diabetes or metabolic syndrome, metformin may less effective at the standard dose. To be effective, doctors may have to first explore glucose control or may have to use a higher dose of metformin," Thor says.


'/>"/>

Contact: Garth Sundem
garth.sundem@ucdenver.edu
University of Colorado Denver
Source:Eurekalert

Related biology news :

1. Study: Death by moonlight? Not always
2. Study: Acidity can change cell membrane properties
3. Penn study: Shutting off neurons helps bullied mice overcome symptoms of depression
4. Rutgers study: Worms may shed light on human ability to handle chronic stress
5. UT study: Chemical in antibacterial soaps may harm nursing babies
6. Study: Pedometer program helps motivate participants to sit less, move more
7. Study: MicroRNA cooperation mutes breast cancer oncogenes
8. Study: Environmental policies matter for growing megacities
9. Study: Widespread test-and-treat HIV policies could increase dangerous drug resistance
10. Study: Probiotics reduce stress-induced intestinal flare-ups
11. Study: Antibiotics are unique assassins
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:11/30/2016)... FRANCISCO and WARSAW, Poland , Nov. 30, 2016 /PRNewswire/ ... It is one of the most crucial aspects of recovery so we need to ... of serious health risks, including heart problems, high blood pressure, stroke, diabetes, and even ... and friends sleep and find a Christmas present that could help them to manage ... ...
(Date:11/29/2016)... VILNIUS, Lithuania , Nov. 29, 2016 ... high-precision biometric identification and object recognition technologies, ... kit (SDK) for fingerprint recognition solutions that ... extract a fingerprint template using less than ... used in compact devices that have limited ...
(Date:11/24/2016)... IRVINE, Calif. , Nov. 23, 2016 ... help endurance athletes and their trainers non-invasively measure ... Variability Index, Pulse Rate, and Respiration Rate in approximately ... Ember enables users easy and immediate access to key ... as part of a training regimen. ...
Breaking Biology News(10 mins):
(Date:12/6/2016)... ... December 06, 2016 , ... Superior Controls, Inc ... today announced the company has successfully completed its 50th consecutive audit. For ... systems integration services to leading companies in life sciences, food and beverage, energy ...
(Date:12/6/2016)... -- Zimmer Biomet Holdings, Inc. (NYSE and SIX: ... of its previously-announced cash tender offers (the "Offers") ... accrued and unpaid interest to, but not including, ... expenses related to the Offers) (the "Maximum Tender ... table below (collectively, the "Notes"). The terms and ...
(Date:12/5/2016)... , Dec. 5, 2016 Axovant Sciences ... biopharmaceutical company focused on the treatment of dementia, today ... for the treatment of Alzheimer,s disease will be presented ... Meeting on Friday, December 9, 2016 in ... show results of both simple and complex measures of ...
(Date:12/5/2016)... December 5, 2016 According ... Market, by Products (Consumable, Instruments, Automated Cell Expansion ... and Stem Cell Research, Cancer, and Cell-Based Research), ... Banks) - Global Revenue, Trends, Growth, Share, Size ... Research, the global cell expansion market is expected ...
Breaking Biology Technology: