A Korean research team has become the first in the world to identify how a fatty acid metabolite produced in the body suppresses cancer cell growth.
A team led by Professor Kim Seyun of the Department of Biological Sciences at the Korea Advanced Institute of Science and Technology (KAIST), in collaboration with Professor Byun Young-joo's team at Korea University's College of Pharmacy, announced Tuesday that they had identified for the first time globally that the body-generated fatty acid metabolite "13-HODE" controls the activity of "mTOR," a key protein in cancer cell growth.
mTOR is a protein that regulates cell growth and energy use. In cancer cells, however, mTOR becomes abnormally activated, functioning as a kind of "growth accelerator pedal." For this reason, cancer treatment research aimed at controlling mTOR is being actively pursued worldwide.
While searching for natural metabolite candidates capable of inhibiting mTOR, the team focused on 13-HODE. The substance is produced when linoleic acid, an essential fatty acid abundant in vegetable oils, is broken down and metabolized in the body.
The research found that 13-HODE binds directly to the active site of the mTOR protein, halting its function in cancer cells. The team verified this through molecular docking simulations (computer-based analysis of molecular interactions) and mass spectrometry (a technology that analyzes the mass and structure of molecules).
The team also discovered that 13-HODE concentrations were extremely low in breast and colon cancer cells. This was because ALOX15, the enzyme that produces 13-HODE, was not properly expressed. Conversely, when ALOX15 activity was enhanced to increase 13-HODE production, mTOR activity decreased and cancer cell growth was suppressed.
The study is significant in that it identified the precise molecular mechanism (the operating principle within living organisms) by which 13-HODE physically binds directly to mTOR to block its function.
"This study is meaningful in revealing that fat metabolites generated within the human body can directly inhibit mTOR, a key protein in cancer growth," Professor Kim said. "It could be used not only for new cancer treatment strategies utilizing fat metabolism, but also for developing therapeutics that regulate mTOR overactivity seen in inflammation and aging processes."
The research findings were published on November 21 in Cell Chemical Biology, an international journal in the field of chemical biology, and were selected as the cover paper.
