title: α-Lipoic acid suppresses migration and invasion via downregulation of cell surface β1-integrin expression in bladder cancer cells.
abstract: Our previous study showed α-lipoic acid (LA) downregulated cell surface β1-integrin expression of v-H-ras-transformed derivative of rat fibroblast with amelioration of their malignant phenotype. Here, we evaluated the ameliorating effect of LA on the malignant characters in H-ras-transformed bladder cancer cells. H-ras mutated bladder cancer line, T24 cells were incubated with LA to evaluate the inhibitory effect on proliferation, migration, invasion and β1-integrin expression. Fluorescence staining of F-actin and western blotting analyses of the related signaling pathways were also performed. LA inhibited the proliferation of T24 cells. Cell adhesion to collagen IV and fibronectin was strikingly inhibited by LA treatment accompanied by downregulation of cell surface but not whole cell β1-integrin expression. LA clearly inhibited cell migration and invasion of T24 cells, which were mimicked by extracellular signal-regulated kinase (ERK) and Akt pathway inhibition. Actually, LA significantly downregulated the phosphorylated ERK and Akt levels. Moreover, LA downregulated phosphorylated focal adhesion kinase level with disappearance of stress fiber formation. Finally, although LA induced the internalization of cell surface β1-integrin, disruption of the raft did not affect the action of LA. Taken together, LA is a promising agent to improve malignant character of bladder cancer cells through regulation of cellular β1-integrin localization.
authors.affiliation: Department of Biochemistry and Applied Biosciences, Faculty of Agriculture, University of Miyazaki, 1-1 Gakuenkibanadai-nishi Miyazaki 889-2192, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Yamasaki
authors.affiliation: Department of Biochemistry and Applied Biosciences, Faculty of Agriculture, University of Miyazaki, 1-1 Gakuenkibanadai-nishi Miyazaki 889-2192, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Iwase
authors.affiliation: Department of Biochemistry and Applied Biosciences, Faculty of Agriculture, University of Miyazaki, 1-1 Gakuenkibanadai-nishi Miyazaki 889-2192, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kawano
authors.affiliation: Department of Biochemistry and Applied Biosciences, Faculty of Agriculture, University of Miyazaki, 1-1 Gakuenkibanadai-nishi Miyazaki 889-2192, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Sakakibara
authors.affiliation: Department of Biochemistry and Applied Biosciences, Faculty of Agriculture, University of Miyazaki, 1-1 Gakuenkibanadai-nishi Miyazaki 889-2192, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Suiko
authors.affiliation: Department of Veterinary Science, Faculty of Agriculture, University of Miyazaki, 1-1 Gakuenkibanadai-nishi Miyazaki 889-2192, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ikeda
authors.affiliation: Department of Biochemistry and Applied Biosciences, Faculty of Agriculture, University of Miyazaki, 1-1 Gakuenkibanadai-nishi Miyazaki 889-2192, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nishiyama
keywords: bladder cancer cells; invasion; migration; α-lipoic acid; β1-integrin