Expression of tumor-associated NADH oxidase (tNOX) affects capsaicin-induced growth inhibition in gastric cancer cells

• Main Authors: Hsi-Min Wang, 汪熙閔
• Other Authors: Pin-Ju Chueh
• Format: Others
• Language: zh-TW
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/53602127752094351100

碩士 === 國立中興大學 === 生物醫學研究所 === 98 === Previous studies had revealed that activity and protein expression of tumor-associated NADH oxidase (tNOX) were closely related to growth of cancer cells. Overexpression tNOX induced transformation in non-cancer cells and knock down tNOX by RNA interference (RNAi) reduced cell growth and migration in HeLa cells. In addition, anti-tumor drugs such as capsaicin, EGCG were found to not only inhibit tNOX activity and protein level but also lead to growth inhibition and apoptosis in cancer cells. However, the correlation between growth inhibition by these drugs and tNOX is not clear. In this project, we studied the correlation between capsaicin-induced growth inhibition and tNOX protein in gastric cancer cell lines. Our results showed that capsaicin treatment induced growth inhibition as well as cell cycle arrest in G0/G1 phase in SNU-1 and TMC-1. We also showed that capsaicin mediated generation of reactive oxygen species (ROS), reduction of mitochondrial membrane potential (MMP), and apoptotic signaling in SNU-1 but not in TMC-1. Base on previous studies demonstrating an association of cell growth and tNOX, we analyzed protein level of tNOX and established that capsaicin was unable to induce tNOX down-regulation in TMC-1. To confirm the role of tNOX in capsaicin-resistant TMC-1 cells, we supressed tNOX gene expression by shRNA and found that TMC-1 cells became more sensitive to capsaicin treatment. In tNOX knock down TMC-1 cells, capsaicin treatment induced greater growth inhibition, as well as generation of ROS, changes in MMP, and apoptosis. Our results suggested that the expression of tNOX in cancer cells was importance for capsaicin-mediated apoptosis.