Genomes and Genes
Summary: Derivatives of PYRUVIC ACID, including its salts and esters.
- Thangaraju M, Karunakaran S, Itagaki S, Gopal E, Elangovan S, Prasad P, et al. Transport by SLC5A8 with subsequent inhibition of histone deacetylase 1 (HDAC1) and HDAC3 underlies the antitumor activity of 3-bromopyruvate. Cancer. 2009;115:4655-66 pubmed publisher..Ectopic expression of the transporter in MCF7 cells led to apoptosis, and the mechanism involved the inhibition of HDAC1/HDAC3. ..
- Wintzell M, Löfstedt L, Johansson J, Pedersen A, Fuxe J, Shoshan M. Repeated cisplatin treatment can lead to a multiresistant tumor cell population with stem cell features and sensitivity to 3-bromopyruvate. Cancer Biol Ther. 2012;13:1454-62 pubmed publisher..1 x IC 50. 3-bromopyruvate might thus be of use in targeting the especially aggressive TIC populations. ..
- Lei C, Lin S, Zhang C, Tao W, Dong W, Hao Z, et al. Effects of high-mobility group box1 on cerebral angiogenesis and neurogenesis after intracerebral hemorrhage. Neuroscience. 2013;229:12-9 pubmed publisher..These findings suggest that HMGB1 may promote angiogenesis and neurogenesis in the late phase of ICH. ..
- Johansson A, Johansson Haque K, Okret S, Palmblad J. Ethyl pyruvate modulates acute inflammatory reactions in human endothelial cells in relation to the NF-kappaB pathway. Br J Pharmacol. 2008;154:1318-26 pubmed publisher..EtP impedes adhesive, secretory and signalling events typical of the early inflammatory response in endothelial cells, suggesting EtP as a possible treatment for acute inflammatory conditions. ..
- Cai B, Brunner M, Wang H, Wang P, Deitch E, Ulloa L. Ethyl pyruvate improves survival in awake hemorrhage. J Mol Med (Berl). 2009;87:423-33 pubmed publisher..Ethyl pyruvate may attenuate systemic inflammatory responses during resuscitation and improve survival in experimental models of awake hemorrhage. ..
- Kim H, Cho I, Kim J, Shin Y, Jeon J, Kim Y, et al. Ethyl pyruvate has an anti-inflammatory effect by inhibiting ROS-dependent STAT signaling in activated microglia. Free Radic Biol Med. 2008;45:950-63 pubmed publisher..These findings offer new therapeutic possibilities for EP based on a better understanding of the mechanism underlying the action of EP. ..
- Matsushita K, Uchida K, Saigusa S, Ide S, Hashimoto K, Koike Y, et al. Glycolysis inhibitors as a potential therapeutic option to treat aggressive neuroblastoma expressing GLUT1. J Pediatr Surg. 2012;47:1323-30 pubmed publisher..We also assessed the efficacy of glycolysis inhibition as an anticancer treatment in neuroblastoma cell lines with altered expression of GLUT1...
- Lee E, Kim H. Inhibitory mechanism of MMP-9 gene expression by ethyl pyruvate in lipopolysaccharide-stimulated BV2 microglial cells. Neurosci Lett. 2011;493:38-43 pubmed publisher..Taken together, our data suggest that the inhibition of MMP-9 may be one of the factors contributing to anti-inflammatory activity of EP in LPS-stimulated microglia. ..
- Di Paola R, Mazzon E, Genovese T, Crisafulli C, Bramanti P, Caminiti R, et al. Ethyl pyruvate reduces the development of zymosan-induced generalized inflammation in mice. Crit Care Med. 2009;37:270-82 pubmed publisher..This study provides evidence that EP attenuates the degree of zymosan-induced shock in mice. ..
- Harvey S, Guerriero E, Charukamnoetkanok N, Piluek J, Schuman J, SundarRaj N. Responses of cultured human keratocytes and myofibroblasts to ethyl pyruvate: a microarray analysis of gene expression. Invest Ophthalmol Vis Sci. 2010;51:2917-27 pubmed publisher..These EP-induced phenotypic changes in myofibroblasts indicate the potential of EP as a therapeutic agent in corneal wound healing. ..
- Choi J, Lee M, Jeong J. Ethyl pyruvate has a neuroprotective effect through activation of extracellular signal-regulated kinase in Parkinson's disease model. Biochem Biophys Res Commun. 2010;394:854-8 pubmed publisher..Thus, EP has neuroprotective effects of EP in Parkinson's disease and its related signaling pathways. ..
- Pereira da Silva A, El Bacha T, Kyaw N, dos Santos R, da Silva W, Almeida F, et al. Inhibition of energy-producing pathways of HepG2 cells by 3-bromopyruvate. Biochem J. 2009;417:717-26 pubmed publisher..These results suggest that the combined action of 3-BrPA on succinate dehydrogenase and on glycolysis, inhibiting steps downstream of the phosphorylation of glucose, play an important role in HepG2 cell death. ..
- Park H, Chung J, Jae H, Kim Y, Son K, Lee M, et al. FDG-PET for evaluating the antitumor effect of intraarterial 3-bromopyruvate administration in a rabbit VX2 liver tumor model. Korean J Radiol. 2007;8:216-24 pubmed..We wanted to investigate the feasibility of using FDG-PET for evaluating the antitumor effect of intraarterial administration of a hexokinase II inhibitor, 3-bromopyruvate (3-BrPA), in a rabbit VX2 liver tumor model...
- Bøgehøj M, Emmeluth C, Overgaard S. Blood flow and microdialysis in the human femoral head. Acta Orthop. 2007;78:56-62 pubmed..The use of MD was established in the human femoral head. Ischemic levels were detected within 2 h of cessation of blood flow in most patients. ..
- Tokumaru O, Kuroki C, Yoshimura N, Sakamoto T, Takei H, Ogata K, et al. Neuroprotective effects of ethyl pyruvate on brain energy metabolism after ischemia-reperfusion injury: a 31P-nuclear magnetic resonance study. Neurochem Res. 2009;34:775-85 pubmed publisher..We suggest the potential involvement of multiple mechanisms of action, such as less acidic intracellular pH, glial production of lactate, and radical scavenging ability. ..
- Huh S, Chung Y, Piao Y, Jin M, Son H, Yoon N, et al. Ethyl pyruvate rescues nigrostriatal dopaminergic neurons by regulating glial activation in a mouse model of Parkinson's disease. J Immunol. 2011;187:960-9 pubmed publisher..The present findings show that EP may inhibit glial-mediated oxidative stress, suggesting that EP may have therapeutic value in the treatment of aspects of Parkinson's disease related to glia-derived oxidative damage. ..
- Fedeli D, Falcioni G, Olek R, Massi M, Cifani C, Polidori C, et al. Protective effect of ethyl pyruvate on msP rat leukocytes damaged by alcohol intake. J Appl Toxicol. 2007;27:561-70 pubmed..The presence of EP considerably reduced superoxide anion production. In conclusion, hypotheses on possible mechanisms of action of EP on rat white blood cells are proposed. ..
- Jang I, Park M, Shin I, Sohn J, Lee H, Chung Y. Ethyl pyruvate has anti-inflammatory and delayed myocardial protective effects after regional ischemia/reperfusion injury. Yonsei Med J. 2010;51:838-44 pubmed publisher..Ethyl pyruvate is associated with a delayed myocardial protective effect after regional I/R injury in an in vivo rat heart model. ..
- Vali M, Liapi E, Kowalski J, Hong K, Khwaja A, Torbenson M, et al. Intraarterial therapy with a new potent inhibitor of tumor metabolism (3-bromopyruvate): identification of therapeutic dose and method of injection in an animal model of liver cancer. J Vasc Interv Radiol. 2007;18:95-101 pubmed..This potent new treatment may prove to be an effective way of treating liver cancer and may become part of a new class of anticancer drugs based on the inhibition of tumor metabolism. ..
- Wang Q, Ding Q, Zhou Y, Gou X, Hou L, Chen S, et al. Ethyl pyruvate attenuates spinal cord ischemic injury with a wide therapeutic window through inhibiting high-mobility group box 1 release in rabbits. Anesthesiology. 2009;110:1279-86 pubmed publisher..These results suggest that EP affords a strong protection against the transient spinal cord ischemic injury with a wide therapeutic window through inhibition of HMGB1 release. ..
- DAVE S, Tilstra J, Matsuoka K, Li F, DeMarco R, Beer Stolz D, et al. Ethyl pyruvate decreases HMGB1 release and ameliorates murine colitis. J Leukoc Biol. 2009;86:633-43 pubmed publisher..Ethyl pyruvate and other strategies to inhibit HMGB1 release and function represent promising interventions in chronic inflammatory diseases. ..
- Santarelli M, Positano V, Giovannetti G, Frijia F, Menichetti L, Ardenkjaer Larsen J, et al. How the signal-to-noise ratio influences hyperpolarized 13C dynamic MRS data fitting and parameter estimation. NMR Biomed. 2012;25:925-34 pubmed publisher..The results of this study may be useful for the establishment of experimental planning and for the optimization of kinetic model estimation as a function of the SNR value. ..
- Su F, Wang Z, Cai Y, Remmelink M, Vincent J. Beneficial effects of ethyl pyruvate in septic shock from peritonitis. Arch Surg. 2007;142:166-71 pubmed..These findings suggest a potential use for EP in the treatment of severe sepsis and septic shock. ..
- Dell Antone P. Targets of 3-bromopyruvate, a new, energy depleting, anticancer agent. Med Chem. 2009;5:491-6 pubmed..The significance of the present findings in concern with a possible therapeutic usefulness of the drug is discussed. ..
- Bennett Guerrero E, Swaminathan M, Grigore A, Roach G, Aberle L, Johnston J, et al. A phase II multicenter double-blind placebo-controlled study of ethyl pyruvate in high-risk patients undergoing cardiac surgery with cardiopulmonary bypass. J Cardiothorac Vasc Anesth. 2009;23:324-9 pubmed publisher..Despite positive results in numerous animal models, the administration of EP does not appear to confer any benefit to cardiac surgical patients undergoing CPB. ..
- Shin S, Han H, Choo S, Yoo B, Park C, Do Y, et al. Hepatic intra-arterial injection of 3-bromopyruvate in rabbit VX2 tumor. Acta Radiol. 2006;47:1036-41 pubmed..416). A single session of intra-arterial injection of 3-BrPA showed no better results in terms of tumor necrosis than that of saline injection in a rabbit VX2 tumor model. ..
- Genovese T, Esposito E, Mazzon E, Di Paola R, Meli R, Caminiti R, et al. Beneficial effects of ethyl pyruvate in a mouse model of spinal cord injury. Shock. 2009;32:217-27 pubmed publisher..Taken together, our results demonstrate that EP treatment reduces the development of inflammation and tissue injury associated with spinal cord trauma. ..
- Olek R, Ziolkowski W, Kaczor J, Wierzba T, Antosiewicz J. Higher hypochlorous acid scavenging activity of ethyl pyruvate compared to its sodium salt. Biosci Biotechnol Biochem. 2011;75:500-4 pubmed..This effect was not related to the presence of ethanol. Better protection of the liver homogenate by ethyl pyruvate was also apparent, despite the fact that cell membrane transport was omitted...
- Cheng B, Liu C, Li W, Fan W, Zhong N, Zhang Y, et al. Ethyl pyruvate improves survival and ameliorates distant organ injury in rats with severe acute pancreatitis. Pancreas. 2007;35:256-61 pubmed..Ethyl pyruvate improves survival and ameliorates distant organ injury of SAP. These beneficial effects of EP are because of the modulation of HMGB1 and other inflammatory cytokine responses. ..
- Tang Z, Yuan S, Hu Y, Zhang H, Wu W, Zeng Z, et al. Over-expression of GAPDH in human colorectal carcinoma as a preferred target of 3-bromopyruvate propyl ester. J Bioenerg Biomembr. 2012;44:117-25 pubmed publisher..The cytotoxic effect of 3-BrOP was associated with its inhibition of GAPDH, and colon cancer cells with loss of p53 were more sensitive to this compound. Our study suggests that GAPDH may be a potential target for colon cancer therapy. ..
- Shen H, Hu X, Liu C, Wang S, Zhang W, Gao H, et al. Ethyl pyruvate protects against hypoxic-ischemic brain injury via anti-cell death and anti-inflammatory mechanisms. Neurobiol Dis. 2010;37:711-22 pubmed publisher..Taken together, our results suggest that EP confers potent neuroprotection against neonatal H-I brain injury via its anti-cell death and anti-inflammatory actions. EP is a potential novel therapeutic agent for neonatal H-I brain injury. ..
- Cruz R, Harada T, Sasatomi E, Fink M. Effects of ethyl pyruvate and other ?-keto carboxylic acid derivatives in a rat model of multivisceral ischemia and reperfusion. J Surg Res. 2011;165:151-7 pubmed publisher..This insight may permit the development of even more effective cytoprotective and anti-inflammatory agents based on the pyruvoyl moiety. ..
- Burgess S, Iizuka K, Jeoung N, Harris R, Kashiwaya Y, Veech R, et al. Carbohydrate-response element-binding protein deletion alters substrate utilization producing an energy-deficient liver. J Biol Chem. 2008;283:1670-8 pubmed..Overall, the shift from fat utilization to pyruvate and lactate utilization resulted in a decrease in the energy of ATP hydrolysis and a hypo-energetic state in the livers of ChREBP(-/-) mice. ..
- Kim J, Ahn K, Kim J, Kim H, Lee J, Lee J, et al. Role of reactive oxygen species-mediated mitochondrial dysregulation in 3-bromopyruvate induced cell death in hepatoma cells : ROS-mediated cell death by 3-BrPA. J Bioenerg Biomembr. 2008;40:607-18 pubmed publisher..Taken together, 3-BrPA induced ATP depletion-dependent necrosis and apoptosis and mitochondrial dysregulation due to ROS production are involved in 3-BrPA-induced cell death in hepatoma cells. ..
- Vali M, Vossen J, Buijs M, Engles J, Liapi E, Ventura V, et al. Targeting of VX2 rabbit liver tumor by selective delivery of 3-bromopyruvate: a biodistribution and survival study. J Pharmacol Exp Ther. 2008;327:32-7 pubmed publisher..The local control of the liver tumor by 3-BrPA resulted in a significant survival benefit...
- Zeng J, Liu J, Yang G, Kelly M, James T, Litt L. Exogenous ethyl pyruvate versus pyruvate during metabolic recovery after oxidative stress in neonatal rat cerebrocortical slices. Anesthesiology. 2007;107:630-40 pubmed..05). EP enters cells, provides pyruvate as a tricarboxylic acid substrate, and is more protective. Although EP provides metabolic protection of adenosine triphosphate levels, it does not maximize antioxidant protection. ..
- Ganapathy Kanniappan S, Geschwind J, Kunjithapatham R, Buijs M, Vossen J, Tchernyshyov I, et al. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is pyruvylated during 3-bromopyruvate mediated cancer cell death. Anticancer Res. 2009;29:4909-18 pubmed..GAPDH pyruvylation by 3BrPA affects its enzymatic function and is the primary intracellular target in 3BrPA mediated cancer cell death. ..
- Fink M. Ethyl pyruvate: a novel treatment for sepsis. Curr Drug Targets. 2007;8:515-8 pubmed..Ethyl pyruvate warrants evaluation as a therapeutic agent for the treatment of sepsis in humans. ..
- Park S, Yi E, Jung M, Lee Y, Kim Y. Ethyl pyruvate, an anti-inflammatory agent, inhibits tumor angiogenesis through inhibition of the NF-?B signaling pathway. Cancer Lett. 2011;303:150-4 pubmed publisher..Activation of NF-?B by vascular endothelial cell growth factor was reduced by EP. Taken together, we suggest that EP may have potential as a new multi-functional drug candidate for anti-angiogenesis and cancer therapy. ..
- Nakano A, Miki H, Nakamura S, Harada T, Oda A, Amou H, et al. Up-regulation of hexokinaseII in myeloma cells: targeting myeloma cells with 3-bromopyruvate. J Bioenerg Biomembr. 2012;44:31-8 pubmed publisher..Furthermore, 3BrPA was able to diminish ATP-dependent ABC transporter activity to restore drug retention in MM cells in the presence of OCs. These results may underpin possible clinical application of 3BrPA in patients with MM. ..
- Dell Antone P. Inactivation of H+-vacuolar ATPase by the energy blocker 3-bromopyruvate, a new antitumour agent. Life Sci. 2006;79:2049-55 pubmed..The findings are discussed with regards to a possible involvement of lysosome destabilization in 3-Br PA induced cell death. ..
- Queirós O, Preto A, Pacheco A, Pinheiro C, Azevedo Silva J, Moreira R, et al. Butyrate activates the monocarboxylate transporter MCT4 expression in breast cancer cells and enhances the antitumor activity of 3-bromopyruvate. J Bioenerg Biomembr. 2012;44:141-53 pubmed publisher..This study supports the potential use of butyrate as adjuvant of 3-BP in the treatment of breast cancer resistant cells, namely ER (-). ..
- Calviño E, Estañ M, Sanchez Martin C, Brea R, de Blas E, Boyano Adánez M, et al. Regulation of death induction and chemosensitizing action of 3-bromopyruvate in myeloid leukemia cells: energy depletion, oxidative stress, and protein kinase activity modulation. J Pharmacol Exp Ther. 2014;348:324-35 pubmed publisher..In summary, 3-BrP cytotoxicity is the result of several combined regulatory mechanisms that might represent important targets to improve therapeutic efficacy. ..
- Yu S, Yoon J, Yang J, Cho E, Kwak M, Jang E, et al. Enhancement of hexokinase II inhibitor-induced apoptosis in hepatocellular carcinoma cells via augmenting ER stress and anti-angiogenesis by protein disulfide isomerase inhibition. J Bioenerg Biomembr. 2012;44:101-15 pubmed publisher..Thus, blockage of PDI activity in combination with HK II inhibitor may be therapeutically useful in HCCs. ..
- Su J, Li X, Cui X, Li Y, Fitz Y, Hsu L, et al. Ethyl pyruvate decreased early nuclear factor-kappaB levels but worsened survival in lipopolysaccharide-challenged mice. Crit Care Med. 2008;36:1059-67 pubmed publisher..Based on the complex role NF-kappaB has regulating both maladaptive and protective host responses, further defining factors that influence EP's effects is important if this agent is considered for patients with or at risk of sepsis. ..
- Fink M. Ethyl pyruvate: a novel anti-inflammatory agent. J Intern Med. 2007;261:349-62 pubmed..EP has been tested in human volunteers and shown to be safe at clinically relevant doses. It remains to be determined whether EP can be used successfully to treat human diseases. ..
- el Sayed S, El Magd R, Shishido Y, Chung S, Diem T, Sakai T, et al. 3-Bromopyruvate antagonizes effects of lactate and pyruvate, synergizes with citrate and exerts novel anti-glioma effects. J Bioenerg Biomembr. 2012;44:61-79 pubmed publisher..3BP induced a caspase-dependent cell death in C6 glioma. 3BP was powerful in decreasing viability of human glioblastoma multiforme cells (U373MG) and C6 glioma in a dose- and time-dependent manner. ..
- Yang R, Zou X, Koskinen M, Tenhunen J. Ethyl pyruvate reduces liver injury at early phase but impairs regeneration at late phase in acetaminophen overdose. Crit Care. 2012;16:R9 pubmed publisher..Inflammation likely contributes to liver damage at an early injurious phase but improves hepatocyte regeneration at a late time point, and prolonged anti-inflammation therapy at a late phase is not beneficial. ..
- Ganapathy Kanniappan S, Geschwind J, Kunjithapatham R, Buijs M, Syed L, Rao P, et al. 3-Bromopyruvate induces endoplasmic reticulum stress, overcomes autophagy and causes apoptosis in human HCC cell lines. Anticancer Res. 2010;30:923-35 pubmed..3-BrPA treatment promotes apoptosis in human HCC cell lines, irrespective of the intracellular response. ..
- Kao K, Fink M. The biochemical basis for the anti-inflammatory and cytoprotective actions of ethyl pyruvate and related compounds. Biochem Pharmacol. 2010;80:151-9 pubmed publisher..The true therapeutic potential of EP and related compounds remains to be elucidated. In this review, some of the biochemical mechanisms, which might be responsible for the pharmacological effects of EP, are discussed. ..
- Lis P, Zarzycki M, Ko Y, Casal M, Pedersen P, Goffeau A, et al. Transport and cytotoxicity of the anticancer drug 3-bromopyruvate in the yeast Saccharomyces cerevisiae. J Bioenerg Biomembr. 2012;44:155-61 pubmed publisher..The sensitivity of yeast to 3-BP is increased considerably by mutations or chemical treatment by buthionine sulfoximine that decrease the intracellular concentration of glutathione. ..
- Chung K, Park J, Kim Y. The role of high-mobility group box-1 in renal ischemia and reperfusion injury and the effect of ethyl pyruvate. Transplant Proc. 2008;40:2136-8 pubmed publisher..From these results, we deduced that the preventive effect of EP on rat kidney ischemia-reperfusion injury was not due to the decreased expression of HMGB1 but the prevention of HMGB1 release. ..
- Cho I, Kim S, Kim J, Kim T, Lee K, Han P, et al. Ethyl pyruvate attenuates kainic acid-induced neuronal cell death in the mouse hippocampus. J Neurosci Res. 2006;84:1505-11 pubmed..In addition, in passive avoidance tests, KA-induced memory impairment was improved markedly by EP. These results suggest that EP has a therapeutic potential for suppressing KA-induced pathogenesis in the brain. ..