Timosaponin AIII Suppresses Hepatocyte Growth Factor-Induced Invasive Activity through Sustained ERK Activation in Breast Cancer MDA-MB-231 Cells. (25th June 2013)

• Record Type: Journal Article
• Authors: Tsai, Chung-Hsin; Yang, Chu-Wen; Wang, Jir-You; Tsai, Yi-Fang; Tseng, Ling-Ming; King, Kuan-Liang; Chen, Wei-Shone; Chiu, Jen-Hwey; Shyr, Yi-Ming
• Other Names: Selvan Senthamil R. Academic Editor.
• Is Part Of: Evidence-based complementary and alternative medicine. Volume 2013(2013)
• Publication Date: 2013-06-25
• Subjects: Alternative medicine -- Periodicals; 615.505
• DOI: 10.1155/2013/421051
• Languages: English
• ISSNs: 1741-427X

Abstract

Abstract : Background . The aim of this study was to investigate the mechanisms by which Timosaponin AIII (TAIII) is able to inhibit HGF-induced invasion activity in the triple negative breast cancer cell line MDA-MB-231. Methods . After pretreatment with different concentrations (10 −6 ~10 −8 M) of TAIII, the cells were treated with hepatocyte growth factor (HGF, 15 ng/mL). At different time intervals after coincubation, various parameters, including the expression of c-Met, ERK, COX2, and MMP-9, which were assessed by Western blotting or by real-time PCR, were analyzed. In addition, invasive activity was also monitored. Results . HGF was found to induce c-MET activation and ERK activation, together with increased COX2 protein expression; these changes were followed by a subsequent increase in invasive activity. TAIII was found to suppress HGF-induced invasive activity and COX2 gene expression in a concentration-dependent manner (10 −6 ~10 −8 M) in parallel with increases in the phosphoforms of c-Met and ERK after TAIII treatment. The mechanisms by which TAIII suppresses HGF-induced invasive activity were demonstrated to include sustained cytoplasmic and nuclear ERK activation; these led to a suppression of nuclear ATF2 activation, which was followed by downregulation of COX2 and MMP-9 transcription. Conclusion . TAIII suppresses HGF-induced invasive activity in MDA-MB-231 cells via sustained ERK activation.