Trehalose suppresses proliferation of cancer cells through inhibition of glycolysis Kunikazu Tanji1, Yasuo Miki1, Tomoh Matsumiya2, Fumiaki Mori1, Tadaatsu Imaizumi2, Ken Itoh3, Koichi Wakabayashi1 1Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan 2Department of Vascular Biology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan 3Department of Stress Response Science, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
ATP generation occurs mainly in two systems in mammalian cells: glycolysis and oxidative phosphorylation. Unlike physiologically normal cells, cancer cells tend to switch from mitochondria-driven oxidative phosphorylation to glycolysis even during sufficient oxygen is available. Glucose is one of natural carbohydrates, as well as an efficient energy source for cancer. Trehalose is also a natural sugar composed of two glucose units, and originally found in a wide range of eukaryotic microorganisms, plants, fungi and insects. Despite extensive research of trehalose in insects and yeast, little attention has been given to the relationship between trehalose and human cancer cells. In this study, we demonstrated that trehalose exhibits inhibitory effect on proliferation of cancer cells mainly due to inefficient ATP generation during glycolysis. Importantly, we indicated that trehalose results in disruption of autophagic flux in cancer cells, although trehalose has been widely used as an autophagy inducer. These results suggest that intravenous injection of trehalose contributes to their increased sensitivity to anti-cancer drugs through inhibition of ATP production to meet their augmented energy demands in cancer cells.
Grant information: JSPS KAKENHI Grant Numbers 17K07088