Inactivation of mTORC1 Pathway by Aqueous Extract of Acanthopanax senticosus

Dysfunction of mammalian target of rapamycin complex 1 (mTORC1), a central regulator of cell growth, is associated with various diseases including obesity and diabetes. Among ? 2,800 plant products used for oriental medicine, Acanthopanax senticosus (A. senticosus) was found to inhibit mTORC1 to phosphorylate S6 kinsase (S6K) in HeLa cells as well as the brain, liver and muscle tissues in diabetic db/db mice. A. senticosus-mediated mTORC1 activity was reversible unlike the prolonged suppression of mTORC1 by rapamycin when HeLa cells were grown in fresh media after the removal of the inhibitors. Autophagy, a self-digestion process occurring in response to nutrient limitation, was activated in HeLa GFP-LC3 cells stably expressing GFP-LC3 by the treatment with the aqueous extract of A. senticosus. The conversion of cytoplasmic LCI into lipidated LCII was increased by fivefold in HeLa GFP-LC3 cells treated with A. senticosus extract. Progression of cell cycle was also attenuated at G2/M phase by the treatment of the aqueous extract of A. senticosus. Taken together, these results suggest that the aqueous extract of A. senticosus possiblyprevents obesity-related diabetes by inhibiting mTOR signaling.