Systemic Treatment with the Antidiabetic Drug Metformin Selectively Impairs p53-Deficient Tumor Cell Growth
Cancer Research Institute of the Slovak Academy of Sciences · University of Pennsylvania · +5 more institutions
Abstract
The effect of the antidiabetic drug metformin on tumor growth was investigated using the paired isogenic colon cancer cell lines HCT116 p53(+/+) and HCT116 p53(-/-). Treatment with metformin selectively suppressed the tumor growth of HCT116 p53(-/-) xenografts. Following treatment with metformin, we detected increased apoptosis in p53(-/-) tumor sections and an enhanced susceptibility of p53(-/-) cells to undergo apoptosis in vitro when subject to nutrient deprivation. Metformin is proposed to function in diabetes treatment as an indirect activator of AMP-activated protein kinase (AMPK). Treatment with AICAR, another AMPK activator, also showed a selective ability to inhibit p53(-/-) tumor growth in vivo. In…
Citation impact
- FWCI
- 19.64
- Percentile
- 100%
- References
- 34
Authors
8- MBMonica BuzzaiCorresponding
Cancer Research Institute of the Slovak Academy of Sciences
- RGRussell G. Jones
Cancer Research Institute of the Slovak Academy of Sciences
- RKRavi K. Amaravadi
Cancer Research Institute of the Slovak Academy of Sciences, University of Pennsylvania
- JJJulian J. Lum
Cancer Research Institute of the Slovak Academy of Sciences
- RJRalph J. DeBerardinis
Children's Hospital of Philadelphia, Cancer Research Institute of the Slovak Academy of Sciences
Topics & keywords
- Metformin
- AMPK
- Autophagy
- AMP-activated protein kinase
- Apoptosis
- Cancer research
- Internal medicine
- Activator (genetics)
- Good health and well-being