Biomaterial Database

Synergistic effect of ERK inhibition on tetrandrine-induced apoptosis in A549 human lung carcinoma cells. 2009

Hyun Sun Cho, and Seung Hee Chang, and Youn Sun Chung, and Ji Young Shin, and Sung Jin Park, and Eun Sun Lee, and Soon Kyung Hwang, and Jung Taek Kwon, and Arash Minai Tehrani, and Minah Woo, and Mi Sook Noh, and Huda Hanifah, and Hua Jin, and Cheng Xiong Xu, and Myung Haing Cho

Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Korea.

Tetrandrine (TET), a bis-benzylisoquinoline alkaloid from the root of Stephania tetrandra, is known to have anti-tumor activity in various malignant neoplasms. However, the precise mechanism by which TET inhibits tumor cell growth remains to be elucidated. The present studies were performed to characterize the potential effects of TET on phosphoinositide 3-kinase/Akt and extracellular signal-regulated kinase (ERK) pathways since these signaling pathways are known to be responsible for cell growth and survival. TET suppressed cell proliferation and induced apoptosis in A549 human lung carcinoma cells. TET treatment resulted in a down-regulation of Akt and ERK phosphorylation in both time-/concentration-dependent manners. The inhibition of ERK using PD98059 synergistically enhanced the TET-induced apoptosis of A549 cells whereas the inhibition of Akt using LY294002 had a less significant effect. Taken together, our results suggest that TET: i) selectively inhibits the proliferation of lung cancer cells by blocking Akt activation and ii) increases apoptosis by inhibiting ERK. The treatment of lung cancers with TET may enhance the efficacy of chemotherapy and radiotherapy and increase the apoptotic potential of lung cancer cells.

UI	MeSH Term	Description	Entries
D008175	Lung Neoplasms	Tumors or cancer of the LUNG.	Cancer of Lung,Lung Cancer,Pulmonary Cancer,Pulmonary Neoplasms,Cancer of the Lung,Neoplasms, Lung,Neoplasms, Pulmonary,Cancer, Lung,Cancer, Pulmonary,Cancers, Lung,Cancers, Pulmonary,Lung Cancers,Lung Neoplasm,Neoplasm, Lung,Neoplasm, Pulmonary,Pulmonary Cancers,Pulmonary Neoplasm
D002277	Carcinoma	A malignant neoplasm made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. It is a histological type of neoplasm and not a synonym for "cancer."	Carcinoma, Anaplastic,Carcinoma, Spindle-Cell,Carcinoma, Undifferentiated,Carcinomatosis,Epithelial Neoplasms, Malignant,Epithelioma,Epithelial Tumors, Malignant,Malignant Epithelial Neoplasms,Neoplasms, Malignant Epithelial,Anaplastic Carcinoma,Anaplastic Carcinomas,Carcinoma, Spindle Cell,Carcinomas,Carcinomatoses,Epithelial Neoplasm, Malignant,Epithelial Tumor, Malignant,Epitheliomas,Malignant Epithelial Neoplasm,Malignant Epithelial Tumor,Malignant Epithelial Tumors,Neoplasm, Malignant Epithelial,Spindle-Cell Carcinoma,Spindle-Cell Carcinomas,Tumor, Malignant Epithelial,Undifferentiated Carcinoma,Undifferentiated Carcinomas
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000972	Antineoplastic Agents, Phytogenic	Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity.	Antineoplastics, Botanical,Antineoplastics, Phytogenic,Agents, Phytogenic Antineoplastic,Botanical Antineoplastics,Phytogenic Antineoplastic Agents,Phytogenic Antineoplastics
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
D044182	Benzylisoquinolines	ISOQUINOLINES with a benzyl substituent.	Benzyl-Isoquinoline,Benzylisoquinoline,Bis-Benzyl-Isoquinoline,Bis-Benzylisoquinoline,Bisbenzylisoquinoline,Bisbenzylisoquinolines,Benzyl-Isoquinolines,Bis-Benzyl-Isoquinolines,Bis-Benzylisoquinolines,Benzyl Isoquinoline,Benzyl Isoquinolines,Bis Benzyl Isoquinoline,Bis Benzyl Isoquinolines,Bis Benzylisoquinoline,Bis Benzylisoquinolines
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
D048049	Extracellular Signal-Regulated MAP Kinases	A mitogen-activated protein kinase subfamily that is widely expressed and plays a role in regulation of MEIOSIS; MITOSIS; and post mitotic functions in differentiated cells. The extracellular signal regulated MAP kinases are regulated by a broad variety of CELL SURFACE RECEPTORS and can be activated by certain CARCINOGENS.	ERK MAP Kinase,ERK MAP Kinases,Extracellular Signal-Regulated Kinase,Extracellular Signal-Regulated Kinases,Extracellular Signal-Regulated MAP Kinase,MAP Kinases, Extracellular Signal-Regulated,Extracellular Signal Regulated Kinase,Extracellular Signal Regulated Kinases,Extracellular Signal Regulated MAP Kinase,Extracellular Signal Regulated MAP Kinases,Kinase, ERK MAP,Kinase, Extracellular Signal-Regulated,Kinases, Extracellular Signal-Regulated,MAP Kinase, ERK,MAP Kinases, Extracellular Signal Regulated,Signal-Regulated Kinase, Extracellular