Journal
SCIENTIFIC REPORTS
Volume 3, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/srep02070
Keywords
-
Categories
Funding
- MIUR [PRIN 2010JS3PMZ_009]
- Italian Ministry of Health
- Italian Association for Cancer Research (AIRC) [6266]
Ask authors/readers for more resources
The anti-hyperglycaemic drug metformin has important anticancer properties as shown by the direct inhibition of cancer cells proliferation. Tumor cells avidly use glucose as a source for energy production and cell building blocks. Critical to this phenotype is the production of glucose-6-phosphate (G6P), catalysed by hexokinases (HK) I and II, whose role in glucose retention and metabolism is highly advantageous for cell survival and proliferation. Here we show that metformin impairs the enzymatic function of HKI and II in Calu-1 cells. This inhibition virtually abolishes cell glucose uptake and phosphorylation as documented by the reduced entrapment of F-18-fluorodeoxyglucose. In-silico models indicate that this action is due to metformin capability to mimic G6P features by steadily binding its pocket in HKII. The impairment of this energy source results in mitochondrial depolarization and subsequent cell death. These results could represent a starting point to open effective strategies in cancer prevention and treatment.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available