title: Hexokinase II inhibitor, 3-BrPA induced autophagy by stimulating ROS formation in human breast cancer cells.
abstract: Hexokinase II (HKII), a key enzyme of glycolysis, is widely over-expressed in cancer cells. 3-bromopyruvate (3-BrPA), an inhibitor of HK II, has been proposed as a specific antitumor agent. Autophagy is a process that regulates the balance between protein synthesis and protein degradation. Autophagy in mammalian systems occurs under basal conditions and can be stimulated by stresses, including starvation, oxidative stress. Therefore, we hypothesized that 3-BrPA could induce autophagy. In the present study, we explored the mechanism of 3-BrPA and its combined action with chloroquine. Our results demonstrate that in MDA-MB-435 and in MDA-MB-231 cells, 3-BrPA induces autophagy, which can be inhibited by chloroquine. Furthermore, the combined treatment synergistically decreased the number of viable cells. Interestingly, the combined treatment triggered apoptosis in MDA-MB-435 cells, while it induced necroptosis in MDA-MB-231 cells. ROS mediated cell death when 3-BrPA and CQ were co-administered. Finally, CQ enhanced the anticancer efficacy of 3-BrPA in vivo. Collectively, our results show that 3-BrPA triggers autophagy, increasing breast cancer cell resistance to 3-BrPA treatment and that CQ enhanced 3-BrPA-induced cell death in breast cancer cells by stimulating ROS formation. Thus, inhibition of autophagy may be an innovative strategy for adjuvant chemotherapy of breast cancer.human skeletal muscle. Efficient Mirk depletion in SU86.86 pancreatic cancer cells by an inducible shRNA decreased expression of eight antioxidant genes. Thus both cancer cells and differentiated myotubes utilize Mirk kinase to relieve oxidative stress.
authors: Faculty of pharmacy, Bengbu Medical College, Bengbu, Anhui, P. R. China.
authors: Qianwen
authors: Q
authors: Zhang
authors: Faculty of pharmacy, Bengbu Medical College, Bengbu, Anhui, P. R. China.
authors: Yuanyuan
authors: Y
authors: Zhang
authors: Faculty of pharmacy, Bengbu Medical College, Bengbu, Anhui, P. R. China.
authors: Pei
authors: P
authors: Zhang
authors: Faculty of pharmacy, Bengbu Medical College, Bengbu, Anhui, P. R. China.
authors: Zhenhua
authors: Z
authors: Chao
authors: Faculty of pharmacy, Bengbu Medical College, Bengbu, Anhui, P. R. China.
authors: Fei
authors: F
authors: Xia
authors: School of Medicine and Public Health, Faculty of Health, University of Newcastle, NSW, Australia.
authors: Chenchen
authors: C
authors: Jiang
authors: School of Medicine and Public Health, Faculty of Health, University of Newcastle, NSW, Australia.
authors: Xudong
authors: X
authors: Zhang
authors: Faculty of pharmacy, Bengbu Medical College, Bengbu, Anhui, P. R. China.
authors: Zhiwen
authors: Z
authors: Jiang
authors: Faculty of pharmacy, Bengbu Medical College, Bengbu, Anhui, P. R. China.
authors: Hao
authors: H
authors: Liu
keywords: 3-BrPA; Apoptosis; Autophagy; CQ; Necroptosis; ROS