title: Glutamine deprivation plus BPTES alters etoposide- and cisplatin-induced apoptosis in triple negative breast cancer cells.
abstract: Glutamine provides cancer cells with the energy required to synthesize macromolecules. Methods which block glutamine metabolism in treatment of breast cancer inhibit oncogenic transformation and tumor growth. We investigated whether inhibiting glutamine metabolism produces effects that are synergistic with those produced by drugs which damage DNA in triple-negative breast cancer cells. HCC1937 and BT-549 breast cancer cells were co-treated with either cisplatin or etoposide in combination with BPTES (a specific inhibitor of glutaminase 1) or exposure to a glutamine-free medium, and the cell proliferation and cell apoptosis were measured by flow cytometry, immunoblotting studies, and CCK-8 assays. The results showed that both glutamine deprivation and BPTES pretreatments increased the toxic effects of cisplatin and etoposide on HCC1937 cells, as demonstrated by their reduced proliferation, increased expression of apoptosis-related proteins (cleaved-PARP, cleaved-caspase 9, and cleaved-caspase 3) and decreased Bcl-2/BAX ratio. However, in BT-549 cells, glutamine deprivation and BPTES treatment increased etoposide-induced apoptosis only when used with higher concentrations of etoposide, and the effect on cisplatin-induced apoptosis was minimal. These results suggest that the anti-cancer effects produced by a combined approach of inhibiting glutamine metabolism and administering common chemotherapeutic agents correlate with the tumor cell type and specific drugs being administered.
authors.affiliation: College of Veterinary Medicine, Sichuan Agricultural University, Ya'an 625014, China.
authors.forename: Lian
authors.initials: L
authors.lastname: Chen
authors.affiliation: College of Veterinary Medicine, Sichuan Agricultural University, Ya'an 625014, China.|Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Ya'an 625014, China.
authors.forename: Hengmin
authors.initials: H
authors.lastname: Cui
authors.affiliation: College of Veterinary Medicine, Sichuan Agricultural University, Ya'an 625014, China.|Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Ya'an 625014, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Fang
authors.affiliation: College of Veterinary Medicine, Sichuan Agricultural University, Ya'an 625014, China.
authors.forename: Huidan
authors.initials: H
authors.lastname: Deng
authors.affiliation: College of Veterinary Medicine, Sichuan Agricultural University, Ya'an 625014, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Kuang
authors.affiliation: College of Veterinary Medicine, Sichuan Agricultural University, Ya'an 625014, China.
authors.forename: Hongrui
authors.initials: H
authors.lastname: Guo
authors.affiliation: College of Veterinary Medicine, Sichuan Agricultural University, Ya'an 625014, China.|Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Ya'an 625014, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Wang
authors.affiliation: College of Veterinary Medicine, Sichuan Agricultural University, Ya'an 625014, China.|Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Ya'an 625014, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhao
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D003470:Culture Media / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000494:pharmacology*; D005260:Female; D005972:Glutaminase / Q000037:antagonists & inhibitors / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D013440:Sulfides / Q000494:pharmacology*; D013830:Thiadiazoles / Q000494:pharmacology*; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D003470:Culture Media; D013440:Sulfides; D013830:Thiadiazoles; C523193:bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide; D005973:Glutamine; D005047:Etoposide; D005972:Glutaminase; D002945:Cisplatin
keywords: BPTES; apoptosis; cisplatin; etoposide; glutamine