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• W2565102430 abstract "// Yu Zhang 1, * , Xin Li 1, * , Shisheng Tan 1 , Xinyu Liu 2 , Xinyu Zhao 2 , Zhu Yuan 2 , Chunlai Nie 2 1 Departmant of Oncology, Guizhou People’s Hospital, Guizhou, China 2 State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, P. R. China * These authors contributed equally to this work Correspondence to: Chunlai Nie, email: niecl1022@hotmail.com Shisheng Tan, email: tssh18018@126.com Keywords: 2-DG, ABT-199, Apoptosis, Bcl-xL, Mcl-1 Received: November 02, 2016      Accepted: December 20, 2016      Published: December 26, 2016 ABSTRACT The regulation of Mcl-1 expression is necessary for the induction of cancer cell apoptosis by ABTs such as ABT-737, ABT-263 and ABT-199. However, the reduction in Mcl-1 expression is not sufficient for initiating cell death in hematopoietic cancer cells with high Bcl-xL expression. Here, we demonstrate that 2-deoxyglucose (2-DG) enhanced the effect of ABT-199 to induce cell apoptosis in hematologic malignancies with up-regulated Bcl-xL expression. Our study revealed that 2-DG could decrease glucose-dependent and Akt-independent Mcl-1 expression, which is mediated by the mechanistic target of rapamycin complex 1 (mTORC1) pathway. Moreover, the combination of 2-DG and ABT-199 triggered c-Jun NH2-terminal kinase (JNK) phosphorylation and subsequent Bcl-xL degradation, whereas 2-DG and ABT-199 alone had little effect on JNK activation. Therefore, the combination of 2-DG and ABT-199 initiated cell death through the reduction of Mcl-1 expression and JNK activation. Our study could provide a clinical theoretical basis for the use of ABT-199 in hematologic malignancies with excessive Bcl-xL expression." @default.
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• W2565102430 date "2016-12-26" @default.
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• W2565102430 title "Mcl-1 expression and JNK activation induces a threshold for apoptosis in Bcl-xL-overexpressing hematopoietic cells" @default.
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• W2565102430 doi "https://doi.org/10.18632/oncotarget.14223" @default.
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