Figure 8.

Mechanism of suppression of FN-induced EMT by cirsiliol in B16F10 metastatic melanoma cells. FN activated PI3K/Akt phosphorylation which, in turn, might have upregulated Twist and Snail (independently or via NFκB p65). Snail itself or through interaction with Twist might have suppressed E-cadherin. Cirsiliol was effective in inhibiting phosphorylation of the PI3K/Akt pathway, which in turn caused downregulation N-cadherin and upregulation of E-cadherin. The signaling pathways indicated within the red dotted line box are already established mechanisms. FN, fibronectin; ⊥, pathways inhibited by cirsiliol; → unidirectional mode of action; ↔, bidirectional mode of action.