Relationship between intracellular ROS production and membrane mobility in curcumin- and tetrahydrocurcumin-treated human gingival fibroblasts and human submandibular gland carcinoma cells

Objective: Curcumin is a well-known chemopreventive agent of oral cancers as well as stomach and intestinal cancers. The relationship between reactive oxygen species (ROS) production and cell membrane mobility was investigated to clarify the pro-oxidant mechanism of curcumin and tetrahydrocurcumin (TH-curcumin). Methods: The intracellular ROS production and membrane mobility by curcumin or TH-curcumin were measured in human submandibular adenocarcinoma cells (HSGs) and human primary gingival fibroblasts (HGFs). ROS and mobility were measured by 5-(and -6)-carboxy-2',7'-dichlorofluorescein diacetate staining and fluorescence recovery after photo bleaching, respectively. Results: Curcumin produced ROS dose-dependently. ROS appeared in the region surrounding the cell membrane. The membrane mobility coefficient of the curcumin-treated cells was significantly lower than that of control cells. The lowered membrane mobility induced by curcumin was reversed by the addition of glutathione, an antioxidant. In contrast, TH-curcumin did not affect the ROS production or the membrane mobility coefficient. The alternations induced by curcumin treated HSG cells were greater than those by HGF cells. Conclusion: The reduction in membrane mobility induced by curcumin was attributed to ROS production. The oxidative effects of curcumin may be related to the structure of the alpha, beta-unsaturated carbonyl moiety as well as the phenolic OH group of this compound.