GSK-3 inhibitors enhance TRAIL-mediated apoptosis in human gastric adenocarcinoma cells. 2018

Yi-Ying Wu, and Chin-Tung Hsieh, and Ying-Ming Chiu, and Shen-Chieh Chou, and Jung-Ta Kao, and Dong-Chen Shieh, and Yi-Ju Lee
Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan.

Resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis has been reported in some cancer cells, including AGS human gastric adenocarcinoma cells. Reducing this resistance might shed light on the treatment of human gastric adenocarcinoma. In this study, we examined whether glycogen synthase kinase-3 (GSK-3) inhibitors can restore TRAIL responsiveness in gastric adenocarcinoma cells. The effect of two GSK-3 inhibitors, SB-415286, and LiCl, on apoptosis signaling of TRAIL in human gastric adenocarcinoma cell lines and primary gastric epithelial cells was analyzed. Both inhibitors can sensitize gastric adenocarcinoma cells, but not primary gastric epithelial cells, to TRAIL-induced apoptosis by increasing caspase-8 activity and its downstream signal transmission. Adding p53 siRNA can downregulate GSK-3 inhibitor-related sensitization to TRAIL-induced apoptosis and caspase-3 activity. GSK-3 inhibitors strongly activate the phosphorylation of JNK. Inhibition of JNK leads to earlier and more intense apoptosis, showing that the activation of JNK may provide anti-apoptotic equilibrium of pro-apoptotic cells. Our observations indicate that GSK-3 inhibitors can sentize AGS gastric adenocarcinoma cells to TRAIL-induced apoptosis. Therefore, in certain types of gastric adenocarcinoma, GSK-3 inhibitor might enhance the antitumor activity of TRAIL and mightbe a promising candidate for the treatment of certain types of gastric adenocarcinoma.

UI MeSH Term Description Entries
D008301 Maleimides Derivatives of maleimide (the structural formula H2C2(CO)2NH) containing a pyrroledione ring where the hydrogen atom of the NH group is replaced with aliphatic or aromatic groups.
D004354 Drug Screening Assays, Antitumor Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals. Anticancer Drug Sensitivity Tests,Antitumor Drug Screens,Cancer Drug Tests,Drug Screening Tests, Tumor-Specific,Dye Exclusion Assays, Antitumor,Anti-Cancer Drug Screens,Antitumor Drug Screening Assays,Tumor-Specific Drug Screening Tests,Anti Cancer Drug Screens,Anti-Cancer Drug Screen,Antitumor Drug Screen,Cancer Drug Test,Drug Screen, Anti-Cancer,Drug Screen, Antitumor,Drug Screening Tests, Tumor Specific,Drug Screens, Anti-Cancer,Drug Screens, Antitumor,Drug Test, Cancer,Drug Tests, Cancer,Screen, Anti-Cancer Drug,Screen, Antitumor Drug,Screens, Anti-Cancer Drug,Screens, Antitumor Drug,Test, Cancer Drug,Tests, Cancer Drug,Tumor Specific Drug Screening Tests
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000230 Adenocarcinoma A malignant epithelial tumor with a glandular organization. Adenocarcinoma, Basal Cell,Adenocarcinoma, Granular Cell,Adenocarcinoma, Oxyphilic,Adenocarcinoma, Tubular,Adenoma, Malignant,Carcinoma, Cribriform,Carcinoma, Granular Cell,Carcinoma, Tubular,Adenocarcinomas,Adenocarcinomas, Basal Cell,Adenocarcinomas, Granular Cell,Adenocarcinomas, Oxyphilic,Adenocarcinomas, Tubular,Adenomas, Malignant,Basal Cell Adenocarcinoma,Basal Cell Adenocarcinomas,Carcinomas, Cribriform,Carcinomas, Granular Cell,Carcinomas, Tubular,Cribriform Carcinoma,Cribriform Carcinomas,Granular Cell Adenocarcinoma,Granular Cell Adenocarcinomas,Granular Cell Carcinoma,Granular Cell Carcinomas,Malignant Adenoma,Malignant Adenomas,Oxyphilic Adenocarcinoma,Oxyphilic Adenocarcinomas,Tubular Adenocarcinoma,Tubular Adenocarcinomas,Tubular Carcinoma,Tubular Carcinomas
D000627 Aminophenols Phenols substituted in any position by an amino group. Hydroxyanilines
D013274 Stomach Neoplasms Tumors or cancer of the STOMACH. Cancer of Stomach,Gastric Cancer,Gastric Neoplasms,Stomach Cancer,Cancer of the Stomach,Gastric Cancer, Familial Diffuse,Neoplasms, Gastric,Neoplasms, Stomach,Cancer, Gastric,Cancer, Stomach,Cancers, Gastric,Cancers, Stomach,Gastric Cancers,Gastric Neoplasm,Neoplasm, Gastric,Neoplasm, Stomach,Stomach Cancers,Stomach Neoplasm
D016159 Tumor Suppressor Protein p53 Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER. p53 Tumor Suppressor Protein,Cellular Tumor Antigen p53,Oncoprotein p53,TP53 Protein,TRP53 Protein,p53 Antigen,pp53 Phosphoprotein,Phosphoprotein, pp53
D017209 Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D047428 Protein Kinase Inhibitors Agents that inhibit PROTEIN KINASES. Protein Kinase Inhibitor,Inhibitor, Protein Kinase,Inhibitors, Protein Kinase,Kinase Inhibitor, Protein,Kinase Inhibitors, Protein

Related Publications

Yi-Ying Wu, and Chin-Tung Hsieh, and Ying-Ming Chiu, and Shen-Chieh Chou, and Jung-Ta Kao, and Dong-Chen Shieh, and Yi-Ju Lee
November 2009, Anticancer research,
Yi-Ying Wu, and Chin-Tung Hsieh, and Ying-Ming Chiu, and Shen-Chieh Chou, and Jung-Ta Kao, and Dong-Chen Shieh, and Yi-Ju Lee
March 2010, Molecular cancer therapeutics,
Yi-Ying Wu, and Chin-Tung Hsieh, and Ying-Ming Chiu, and Shen-Chieh Chou, and Jung-Ta Kao, and Dong-Chen Shieh, and Yi-Ju Lee
August 2003, Cancer research and treatment,
Yi-Ying Wu, and Chin-Tung Hsieh, and Ying-Ming Chiu, and Shen-Chieh Chou, and Jung-Ta Kao, and Dong-Chen Shieh, and Yi-Ju Lee
January 2011, Phytotherapy research : PTR,
Yi-Ying Wu, and Chin-Tung Hsieh, and Ying-Ming Chiu, and Shen-Chieh Chou, and Jung-Ta Kao, and Dong-Chen Shieh, and Yi-Ju Lee
June 2019, BMC complementary and alternative medicine,
Yi-Ying Wu, and Chin-Tung Hsieh, and Ying-Ming Chiu, and Shen-Chieh Chou, and Jung-Ta Kao, and Dong-Chen Shieh, and Yi-Ju Lee
November 2007, Cancer letters,
Yi-Ying Wu, and Chin-Tung Hsieh, and Ying-Ming Chiu, and Shen-Chieh Chou, and Jung-Ta Kao, and Dong-Chen Shieh, and Yi-Ju Lee
April 2009, The Journal of nutritional biochemistry,
Yi-Ying Wu, and Chin-Tung Hsieh, and Ying-Ming Chiu, and Shen-Chieh Chou, and Jung-Ta Kao, and Dong-Chen Shieh, and Yi-Ju Lee
July 2010, International journal of oncology,
Yi-Ying Wu, and Chin-Tung Hsieh, and Ying-Ming Chiu, and Shen-Chieh Chou, and Jung-Ta Kao, and Dong-Chen Shieh, and Yi-Ju Lee
May 2023, ACS omega,
Yi-Ying Wu, and Chin-Tung Hsieh, and Ying-Ming Chiu, and Shen-Chieh Chou, and Jung-Ta Kao, and Dong-Chen Shieh, and Yi-Ju Lee
December 2009, International journal of molecular sciences,
Copied contents to your clipboard!