Navigation Links
Study questions anti-cancer mechanisms of drug tested in clinical trials
Date:1/13/2014

CINCINNATI The diabetes drug metformin is also being tested in numerous clinical trials for treating different cancers, and several studies point to its apparent activation of a molecular regulator of cell metabolism called AMPK to suppress tumor growth.

But new research appearing the week of Jan. 13 in Proceedings of the National Academy of Sciences (PNAS) suggests that activation of AMPK may actually fuel cancer growth. Researchers from Cincinnati Children's Hospital Medical Center who led the study also recommend that clinicians testing metformin for cancer treatment consider a careful re-evaluation of their clinical data.

The researchers report on extensive laboratory tests that conclude metformin does stop cancer, although not by activating AMPK. Instead, in tests involving glioma brain cancer cells, the authors found that metformin inhibits a different molecule called mammalian target of rapamycin (mTOR) that has been linked to many other cancers.

In the body, metformin also suppresses the actions of insulin and insulin-like growth factors two molecules that support cancer growth and also likely independent of AMPK, according to Biplab Dasgupta, PhD, principal investigator and a researcher in the Division of Hematology/Oncology at Cincinnati Children's.

"Our findings do not suggest that clinical trials using metformin should be stopped. Metformin appears to be a very useful drug, but the drug's mechanism of cancer suppression is not clear," Dr. Dasgupta said. "However, our findings unveil a potential role for AMPK as a tumor growth supporter, not a suppressor, in the type of cancer that we study. This is why clinicians using metformin in clinical trials should use caution during data interpretation."

Dasgupta and his research colleagues decided to tackle the question of metformin's anti-cancer properties because some studies point to AMPK as a tumor suppressor, while others have suggested it can promote tumor growth. Ultimately, an accurate understanding of AMPK's role and how a drug like metformin does stop cancer will likely be important to continued improvement of targeted cancer therapies, he said.

AMPK is a metabolic enzyme that acts as a key sensor of energy levels in cells. It controls a number of metabolic pathways that allow cells to regulate their energy usage and survival under physiological stress. Cancer cells modify their metabolism to maintain their growth and survival in the stressful environment of the tumor.

To determine how AMPK and metformin react in the context of cancer, the researchers conducted tests using glioblastoma, a highly lethal brain cancer with no cure. Their experiments involved laboratory cell cultures of human glioblastoma cells and glioblastoma tumors transplanted in mice to obtain results in a living organism.

Compared to normal human and mouse tissue, the researchers found that AMPK was highly active in human and mouse glioblastoma cells. This led them to question whether the anti-cancer properties of metformin were independent of AMPK, and instead directed to other molecular pathways.

The researchers then treated human glioblastoma cells with metformin and conducted a series of genetic tests to determine the molecular pathways it uses to stop the cancer growth. Those tests showed clearly that metformin directly inhibited the mTOR pathway (and the cancer) by promoting the interaction of two upstream molecules that stop the pathway's function.

To further verify that AMPK activation by metformin is not involved in stopping the growth of cancer, the researchers also treated the glioblastoma cells with a more specific AMPK activating compound called A769662 that directly binds to AMPK. The treatment did not kill glioblastoma cells, according to the authors.

Dasgupta and his colleagues are continuing their research by testing direct genetic inhibition of AMPK to see how it impacts human glioblastoma cells. Although that research still has to be completed and the results verified, he said preliminary indications are that blocking AMPK appears to kill a significant number of the glioblastoma cells.


'/>"/>

Contact: Nick Miller
nicholas.miller@cchmc.org
513-803-6035
Cincinnati Children's Hospital Medical Center
Source:Eurekalert

Related medicine news :

1. Study Suggests Vaccine May Help Kids With Brain Cancer
2. Study reveals how cancer drug causes diabetic-like state
3. Coffee Drinking in Pregnancy Wont Lead to Sleepless Baby: Study
4. Lower GI problems plague many with rheumatoid arthritis, Mayo Clinic study finds
5. Veggies Like Broccoli, Cabbage May Help Fight Breast Cancer: Study
6. No Added Cancer Risk From Hip Replacement Materials: Study
7. Reported Decline in U.S. Pneumonia Deaths May Be False: Study
8. Early Study Finds Some Promise for Lung Cancer Vaccine
9. Narcissists Often Ace Job Interviews, Study Finds
10. Sexual objectification of female artists in music videos exists regardless of race, MU study finds
11. Soy may alleviate hot flashes in menopause, large-scale study finds
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/27/2016)... ... June 27, 2016 , ... "FCPX editors can now reveal their ... Cut Pro X," said Christina Austin - CEO of Pixel Film Studios. , ... Pro X users can now reveal the media of their split screens with ...
(Date:6/26/2016)... ... ... Quality metrics are proliferating in cancer care, and are derived from many ... the beholder, according to experts who offered insights and commentary in the current issue ... the full issue, click here . , For the American Society of Clinical ...
(Date:6/26/2016)... ... June 26, 2016 , ... ... have been diagnosed with endometriosis. These women need a treatment plan to not ... comprehensive approach that can help for preservation of fertility and ultimately achieving a ...
(Date:6/25/2016)... ... 25, 2016 , ... First Choice Emergency Room , the largest network ... the Medical Director of its new Mesquite-Samuell Farm facility. , “We are pleased ... location,” said Dr. James M. Muzzarelli, Executive Medical Director of First Choice Emergency Room. ...
(Date:6/24/2016)... ... 2016 , ... A recent article published June 14 on E ... goes on to state that individuals are now more comfortable seeking to undergo not ... as calf and cheek reduction. The Los Angeles area medical group, Beverly Hills Physicians ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... , June 23, 2016  Guerbet announced today that ... Supplier Horizon Award . One of ... was recognized for its support of Premier members through ... clinical excellence, and commitment to lower costs. ... this recognition of our outstanding customer service from Premier," ...
(Date:6/23/2016)... 2016 Research and Markets has ... Global Analysis (United States, China, Japan, Brazil, United Kingdom, ... their offering. Surgical ... business planners, provides surgical procedure volume data in a ... an in-depth analysis of growth drivers and inhibitors, including ...
(Date:6/23/2016)... , June 23, 2016 The ... it continues to present great opportunities to investors. Stock-Callers.com ... today: Intrexon Corp. (NYSE: XON ), Vertex ... Inc. (NASDAQ: ARNA ), and Regeneron Pharmaceuticals ... these stocks and receive your complimentary trade alerts at: ...
Breaking Medicine Technology: