Arecoline inhibits the growth of 3T3-L1 preadipocytes via AMP-activated protein kinase and reactive oxygen species pathways.

The present study was designed to investigate the pathways involved in the effect of betel nut arecoline on cell viability in 3T3-L1 preadipocytes. Arecoline, but not arecaidine or guvacine, inhibited preadipocyte viability in a concentration- and time-dependent manner. Arecoline arrested preadipocyte growth in the G2/M phase of the cell cycle; decreased the total levels of cyclin-dependent kinase 1 (CDK1), p21, and p27 proteins; increased p53 and cyclin B1 protein levels; and had no effect on CDK2 protein levels. These results suggested that arecoline selectively affected a particular CDK subfamily. Arecoline inhibited AMP-activated protein kinase (AMPK) activity; conversely, the AMPK activator, AICAR, blocked the arecoline-induced inhibition of cell viability. Pre-treatment with the antioxidant, N-acetylcysteine, prevented the actions of arecoline on cell viability, G2/M growth arrest, reactive oxygen species (ROS) production, and the levels of CDK1, p21, p27, p53, cyclin B1, and phospho-AMPK proteins. These AMPK- and ROS-dependent effects of arecoline on preadipocyte growth may be related to the mechanism underlying the modulatory effect of arecoline on body weight.
Competing Interests: Landseed General Hospital provided support in the form of salaries for author YCK. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.