Glutamine deprivation plus BPTES alters etoposide- and cisplatin-induced apoptosis in triple negative breast cancer cells
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Lian Chen1, Hengmin Cui1,2, Jing Fang1,2, Huidan Deng1, Ping Kuang1, Hongrui Guo1, Xun Wang1,2, Ling Zhao1,2
1College of Veterinary Medicine, Sichuan Agricultural University, Ya’an 625014, China
2Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Ya’an 625014, China
Hengmin Cui, email: [email protected]
Keywords: glutamine, apoptosis, BPTES, cisplatin, etoposide
Received: April 19, 2016 Accepted: June 30, 2016 Published: July 13, 2016
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.
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