Researchers from the University of Cincinnati College of Medicine have discovered that the metabolism of cells plays an important role in the ability to run the survival of the program, called autophagy, an undesirable side effect of some anti-cancer drugs that help tumor cells grow into new tumors.
The results, published in the online edition of the journal Cell Reports, provide new ideas about the use of cell metabolism and the effect on the tumor cells that survive the treatment.
"Cells adapt to starvation by increasing autophagy, when a cell is powered basically a cellular contents and processes to maintain the basic processes. This process is regulated on the targeting rapamycin (mTOR) and AMP-activated protein kinase (AMPK), - explains Carol Mercer, Associate Professor of hematological oncology. - Drugs that target the mTOR or activating of AMPK, are used in the clinic for some types of cancer, and the need to understand how they affect the way the survival of tumor cells. "
"We found that cellular metabolism significantly affect the ability to initiate the process of autophagy, and the function of the mitochondrial complex I is an important factor in the initiation, amplification and duration of response, - she says. - We show that the diabetes drug phenformin, metformin and genetic defects in complex I alter cellular metabolism to glycolysis and inhibit mTOR inhibitors capable of accelerating autophagy. Our data demonstrate the importance of autophagy in the regulation of metabolism, improve understanding of clinically important drugs are important for cancer, and suggest new strategies to regulate autophagy. "
Mercer and her staff worked mainly with cultured cells to understand how the metabolism regulates autophagy, with the advantage of defining a strategy for manipulating patients. The work was based on preclinical studies in animal models Hal Elnakata Thomas, first author research department, who found that the combination of mTOR inhibitors effective in treating hepatocellular carcinoma (liver cancer).
"Our data show a dynamic and metabolic regulation of autophagy and offer a novel therapeutic strategy for the treatment of cancer, neurodegenerative and mitochondrial diseases - said Mercer. - It is necessary to further explore the causes of these mechanisms and the consequences of how metabolic regulation of autophagy may be used in the clinic. "