title: A novel glutaminase inhibitor-968 inhibits the migration and proliferation of non-small cell lung cancer cells by targeting EGFR/ERK signaling pathway.
abstract: Metabolic reprogramming is critical for cancer cell proliferation. Glutaminolysis which provides cancer cells with bioenergetics and intermediates for macromolecular synthesis have been intensively studied in recent years. Glutaminase C (GAC) is the first and rate-limiting enzyme in glutaminolysis and plays important roles in cancer initiation and progression. We previously screened a small molecule named 968, a specific inhibitor of GAC, to block the proliferation of human breast cancer cells. In this study, we found that 968 effectively inhibited NSCLC cell proliferation and migration and arrested G0/G1 phase of cell cycle. Furthermore, we demonstrated that 968 inhibited the EGFR/ERK pathway via decreasing the expression of EGFR and phospho-ERK. Apart from this, we discovered that 968 treatment induced autophagy to protect cells against apoptosis and the combination of 968 with autophagy inhibitor Chloroquine (CQ) had synergistic effects on the growth of NSCLC cells. Thus, our study pointed out a new therapeutic strategy for NSCLC treatment by combination of 968 with CQ.
authors.affiliation: Institute of Translational Medicine, Nanchang University, Nanchang City, Jiangxi 330031, China.|School of Life Sciences, Nanchang University, Nanchang City, Jiangxi 330031, China.
authors.forename: Tianyu
authors.initials: T
authors.lastname: Han
authors.affiliation: Institute of Translational Medicine, Nanchang University, Nanchang City, Jiangxi 330031, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Guo
authors.affiliation: Research Institute of Applied Biology, Shanxi University, Taiyuan, Shanxi, 030006, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Institute of Translational Medicine, Nanchang University, Nanchang City, Jiangxi 330031, China.
authors.forename: Mingxi
authors.initials: M
authors.lastname: Gan
authors.affiliation: Institute of Translational Medicine, Nanchang University, Nanchang City, Jiangxi 330031, China.
authors.forename: Caifeng
authors.initials: C
authors.lastname: Xie
authors.affiliation: Institute of Translational Medicine, Nanchang University, Nanchang City, Jiangxi 330031, China.
authors.forename: Jian-Bin
authors.initials: JB
authors.lastname: Wang
mesh_terms: D001343:Autophagy / Q000187:drug effects; D000071186:Beclin-1 / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D066246:ErbB Receptors / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005972:Glutaminase / Q000037:antagonists & inhibitors*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000071186:Beclin-1; D004791:Enzyme Inhibitors; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases; D005972:Glutaminase
keywords: autophagy; epidermal growth factor receptor; glutaminase inhibitor; glutamine metabolism; non-small cell lung cancer