Figure 9
Schematic representation of the arecoline-stimulated signaling pathways for detachment and apoptosis of HA22T/VGH cells. Arecoline treatment decreases IL-6 levels, but does not change gp130 of IL-6 receptor. In addition, phosphorylation/activation of STAT3, which provides protection against anoikis, is inhibited and levels of its downstream signals IL-6, Bcl-2, and Bcl-XL are decreased, while Bax levels, mitochondrial cytochrome c release, caspase-9 levels, and caspase-3 activity are increased. Phosphorylation/activation of p190RhoGAP, a RhoA inhibitor, and its upstream regulator, SHP2, are inhibited, while the activation/cleavage of Rock-1, a RhoA downstream kinase, and actin stress fiber formation are increased, contributing to anoikis.