Cucurbitacin I induces pro-death autophagy in A549 cells via the ERK-mTOR-STAT3 signaling pathway. 2018

Yinyun Ni, and Sisi Wu, and Xiangxiu Wang, and Guonian Zhu, and Xuemei Chen, and Yu Ding, and Wei Jiang
Research Core Facility, West China Hospital, Sichuan University, Chengdu, Sichuan, P. R. China.

Natural products are a great source of cancer chemotherapeutic agents. In the present study, the anticancer effects of cucurbitacin I on A549 cells were investigated. Cucurbitacin I decreased cell viability, inhibited colony formation, and induced apoptosis in A549 cells. Cucurbitacin I caused accumulation of autophagosome and dose-dependent expression of LC3II protein. Autophagy inhibitors 3-methyladenine (3-MA) inhibited autophagy induced by cucurbitacin I and relieved cucurbitacin I-triggered cell death and apoptosis in A549 Cells. Cucurbitacin I treatment inhibits the ERK activation and the downstream phosphorylation level of mTOR and STAT3, but not the PI3K/Akt pathway. Furthermore, treatment with the mTOR activator MHY-1485, which also suppressed cucurbitacin I-induced LC3II expression, and also reversed cucurbitacin I-induced cell death and apoptosis. Taken together, these results suggest that cucurbitacin I induced pro-death autophagy through ERK/mTOR/STAT3 signaling cascade in A549 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
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000072283 A549 Cells An immortalized cell line derived from human ADENOCARCINOMA, ALVEOLAR basal epithelial cells isolated from the lungs of a male patient in 1972. The cell line is positive for KERATIN, can synthesize LECITHIN, and contains high levels of POLYUNSATURATED FATTY ACIDS in its PLASMA MEMBRANE. It is used as a model for PULMONARY ALVEOLI function and virus infections, as a TRANSFECTION host, and for PRECLINICAL DRUG EVALUATION. A549 Cell Line,A549 Cell,A549 Cell Lines,Cell Line, A549,Cell Lines, A549,Cell, A549,Cells, A549
D001343 Autophagy The segregation and degradation of various cytoplasmic constituents via engulfment by MULTIVESICULAR BODIES; VACUOLES; or AUTOPHAGOSOMES and their digestion by LYSOSOMES. It plays an important role in BIOLOGICAL METAMORPHOSIS and in the removal of bone by OSTEOCLASTS. Defective autophagy is associated with various diseases, including NEURODEGENERATIVE DISEASES and cancer. Autophagocytosis,ER-Phagy,Lipophagy,Nucleophagy,Reticulophagy,Ribophagy,Autophagy, Cellular,Cellular Autophagy,ER Phagy
D014315 Triterpenes A class of terpenes (the general formula C30H48) formed by the condensation of six isoprene units, equivalent to three terpene units. Triterpene,Triterpenoid,Triterpenoids
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D015972 Gene Expression Regulation, Neoplastic Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue. Neoplastic Gene Expression Regulation,Regulation of Gene Expression, Neoplastic,Regulation, Gene Expression, Neoplastic
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
D048052 Mitogen-Activated Protein Kinase 3 A 44-kDa extracellular signal-regulated MAP kinase that may play a role the initiation and regulation of MEIOSIS; MITOSIS; and postmitotic functions in differentiated cells. It phosphorylates a number of TRANSCRIPTION FACTORS; and MICROTUBULE-ASSOCIATED PROTEINS. Extracellular Signal-Regulated Kinase 1,ERK1 Kinase,MAPK3 Mitogen-Activated Protein Kinase,Meiosis-Activated Myelin Basic Protein Kinase p44(mpk),Microtubule-Associated Protein-2 Kinase,PSTkinase p44mpk,Protein-Serine-Threonine Kinase p44(mpk),p44 MAPK,Extracellular Signal Regulated Kinase 1,Kinase, ERK1,Kinase, Microtubule-Associated Protein-2,MAPK3 Mitogen Activated Protein Kinase,Microtubule Associated Protein 2 Kinase,Mitogen Activated Protein Kinase 3,p44mpk, PSTkinase
D049109 Cell Proliferation All of the processes involved in increasing CELL NUMBER including CELL DIVISION. Cell Growth in Number,Cellular Proliferation,Cell Multiplication,Cell Number Growth,Growth, Cell Number,Multiplication, Cell,Number Growth, Cell,Proliferation, Cell,Proliferation, Cellular

Related Publications

Yinyun Ni, and Sisi Wu, and Xiangxiu Wang, and Guonian Zhu, and Xuemei Chen, and Yu Ding, and Wei Jiang
July 2016, Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology,
Yinyun Ni, and Sisi Wu, and Xiangxiu Wang, and Guonian Zhu, and Xuemei Chen, and Yu Ding, and Wei Jiang
November 2015, Molecular carcinogenesis,
Yinyun Ni, and Sisi Wu, and Xiangxiu Wang, and Guonian Zhu, and Xuemei Chen, and Yu Ding, and Wei Jiang
July 2014, Scientific reports,
Yinyun Ni, and Sisi Wu, and Xiangxiu Wang, and Guonian Zhu, and Xuemei Chen, and Yu Ding, and Wei Jiang
December 2014, Molecular medicine reports,
Yinyun Ni, and Sisi Wu, and Xiangxiu Wang, and Guonian Zhu, and Xuemei Chen, and Yu Ding, and Wei Jiang
December 2016, Journal of drug targeting,
Yinyun Ni, and Sisi Wu, and Xiangxiu Wang, and Guonian Zhu, and Xuemei Chen, and Yu Ding, and Wei Jiang
November 2012, Journal of virology,
Yinyun Ni, and Sisi Wu, and Xiangxiu Wang, and Guonian Zhu, and Xuemei Chen, and Yu Ding, and Wei Jiang
January 2020, Cancer management and research,
Yinyun Ni, and Sisi Wu, and Xiangxiu Wang, and Guonian Zhu, and Xuemei Chen, and Yu Ding, and Wei Jiang
December 2016, Toxicology letters,
Yinyun Ni, and Sisi Wu, and Xiangxiu Wang, and Guonian Zhu, and Xuemei Chen, and Yu Ding, and Wei Jiang
December 2019, Bioscience reports,
Yinyun Ni, and Sisi Wu, and Xiangxiu Wang, and Guonian Zhu, and Xuemei Chen, and Yu Ding, and Wei Jiang
April 2021, Life sciences,
Copied contents to your clipboard!