Research Paper Volume 11, Issue 23 pp 11624—11639

Stimulation of MMP-9 of oral epithelial cells by areca nut extract is related to TGF-β/Smad2-dependent and –independent pathways and prevented by betel leaf extract, hydroxychavicol and melatonin

Figure 2. Role of TGF-β and Smad2 signaling on ANE-induced MMP-9 expression/secretion of oral epithelial cells. (A) Stimulation of TGF-β protein expression of SAS cells by ANE (800 μg/ml) and its attenuation by SB431542 (1 and 5 μM), (B) ANE (100-800 μg/ml) stimulated Smad2 phosphorylation of SAS cells after 24-hr of exposure, (C) ANE (50-800 μg/ml) stimulated Smad2 phosphorylation of GK after 24-hr of exposure, (D) SB431542 (1 and 5 μM) attenuated the ANE (800 μg/ml)-induced p-Smad2 expression of SAS cells, (E) SB431542 attenuated the ANE (800 μg/ml)-induced p-Smad2 expression of GK, (F) SB431542 prevented the ANE (800 μg/ml)-induced MMP-9 secretion of SAS cells, (G) SB431542 prevented the ANE (800 μg/ml)-induced MMP-9 secretion of GK, (H) SB431542 showed little effect on ANE (800 μg/ml)-induced cytotoxicity of SAS cells (as % of control, 100%). *denotes statistically significant difference when compared with control. #denotes statistically significant difference when compared with ANE-treated group.