PMID- 27163639 OWN - NLM STAT- MEDLINE DCOM- 20170509 LR - 20181202 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 475 IP - 1 DP - 2016 Jun 17 TI - 3-Bromopyruvate and sodium citrate induce apoptosis in human gastric cancer cell line MGC-803 by inhibiting glycolysis and promoting mitochondria-regulated apoptosis pathway. PG - 37-43 LID - S0006-291X(16)30708-2 [pii] LID - 10.1016/j.bbrc.2016.04.151 [doi] AB - Cancer cells are mainly dependent on glycolysis to generate adenosine triphosphate (ATP) and intermediates required for cell growth and proliferation. Thus, inhibition of glycolysis might be of therapeutic value in antitumor treatment. Our previously studies had found that both 3-bromopyruvate (BP) and sodium citrate (SCT) can inhibit tumor growth and proliferation in vitro and in vivo. However, the mechanism involved in the BP and SCT mediated antitumor activity is not entirely clear. In this work, it is demonstrated that BP inhibits the enzyme hexokinase (HK) activity and SCT suppresses the phosphofructokinase (PFK) activity respectively, both the two agents decrease viability, ATP generation and lactate content in the human gastric cancer cell line MGC-803. These effects are directly correlated with blockage of glycolysis. Furthermore, BP and SCT can induce the characteristic manifestations of mitochondria-regulated apoptosis, such as down-regulation of anti-apoptosis proteins Bcl-2 and Survivin, up-regulation of pro-apoptosis protein Bax, activation of caspase-3, as well as leakage of cytochrome c (Cyt-c). In summary, our results provided evidences that BP and SCT inhibit the MGC-803 cells growth and proliferation might be correlated with inhibiting glycolysis and promoting mitochondria-regulated apoptosis. CI - Copyright (c) 2016 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Guo, Xingyu AU - Guo X AD - Department of Gastrointestinal and Gland Surgery, The First Affiliated Hospital of Guangxi Medical University, 6 ShuangYong Road, Nanning, Guangxi 530021, China. FAU - Zhang, Xiaodong AU - Zhang X AD - Department of Gastrointestinal and Gland Surgery, The First Affiliated Hospital of Guangxi Medical University, 6 ShuangYong Road, Nanning, Guangxi 530021, China. FAU - Wang, Tingan AU - Wang T AD - Department of Gastrointestinal and Gland Surgery, The First Affiliated Hospital of Guangxi Medical University, 6 ShuangYong Road, Nanning, Guangxi 530021, China. Electronic address: moonsonlife@yahoo.com. FAU - Xian, Shulin AU - Xian S AD - Department of Gastrointestinal and Gland Surgery, The First Affiliated Hospital of Guangxi Medical University, 6 ShuangYong Road, Nanning, Guangxi 530021, China. FAU - Lu, Yunfei AU - Lu Y AD - Department of Gastrointestinal and Gland Surgery, The First Affiliated Hospital of Guangxi Medical University, 6 ShuangYong Road, Nanning, Guangxi 530021, China. Electronic address: doctorlife@126.com. LA - eng PT - Journal Article DEP - 20160506 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Antineoplastic Agents) RN - 0 (Citrates) RN - 0 (Pyruvates) RN - 1Q73Q2JULR (Sodium Citrate) RN - 63JMV04GRK (bromopyruvate) SB - IM MH - Antineoplastic Agents/*pharmacology MH - Apoptosis/*drug effects MH - Cell Line, Tumor MH - Citrates/*pharmacology MH - Gastric Mucosa/metabolism MH - Glycolysis/*drug effects MH - Humans MH - Mitochondria/drug effects/metabolism/pathology MH - Pyruvates/*pharmacology MH - Sodium Citrate MH - Stomach/*drug effects/pathology MH - Stomach Neoplasms/*drug therapy/metabolism/pathology OTO - NOTNLM OT - 3-Bromopyruvate OT - Apoptosis OT - Energetic metabolism OT - Gastric carcinoma OT - Glycolysis OT - Sodium citrate EDAT- 2016/05/11 06:00 MHDA- 2017/05/10 06:00 CRDT- 2016/05/11 06:00 PHST- 2016/04/16 00:00 [received] PHST- 2016/04/27 00:00 [accepted] PHST- 2016/05/11 06:00 [entrez] PHST- 2016/05/11 06:00 [pubmed] PHST- 2017/05/10 06:00 [medline] AID - S0006-291X(16)30708-2 [pii] AID - 10.1016/j.bbrc.2016.04.151 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2016 Jun 17;475(1):37-43. doi: 10.1016/j.bbrc.2016.04.151. Epub 2016 May 6.