3-bromopyruvate: Targets and outcomes

Shoshan, Maria C.

doi:10.1007/s10863-012-9419-2

Cited by 130 publications

(104 citation statements)

References 74 publications

(115 reference statements)

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“…3-BrPA has recently become a popular drug among research scholars worldwide (21). This drug is a glycolytic inhibitor that acts via hexokinase II and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and plays a critical role in apoptosis induced by intracellular ATP depletion.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory effects of 3-bromopyruvate in human nasopharyngeal carcinoma cells

et al. 2015

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Abstract. Tumor cells depend on aerobic glycolysis for adenosine triphosphate (ATP) production, which is therefore targeted by therapeutic agents. The compound 3-bromopyruvate (3-BrPA), a strong alkylating agent and hexokinase inhibitor, inhibits tumor cell glycolysis and the production of ATP, causing apoptosis. 3-BrPA induces apoptosis of nasopharyngeal carcinoma (NPC) cell lines HNE1 and CNE-2Z, which may be related to its molecular mechanisms. In the present study, we investigated the effects of 3-BrPA on the viability, reactive oxygen species (ROS), apoptosis and other types of programmed cell death in NPC cells in vitro and in vivo. PI staining showed significant apoptosis in NPC cells accompanied by the overproduction of ROS and downregulation of mitochondrial membrane potential (MMP, ΔΨm) by 3-BrPA. However, the ROS scavenger N-acetyl-L-cysteine (NAC) significantly reduced 3-BrPA-induced apoptosis by decreasing ROS and facilitating the recovery of MMP. We elucidated the molecular mechanisms underlying 3-BrPA activity and found that it caused mitochondrial dysfunction and ROS production, leading to necroptosis of NPC cells. We investigated the effects of the caspase inhibitor z-VAD-fmk, which inhibits apoptosis but promotes death domain receptor (DR)-induced NPC cell necrosis. Necrostatin-1 (Nec-1) inhibits necroptosis, apparently via a DR signaling pathway and thus abrogates the effects of z-VAD-fmk. In addition, we demonstrated the effective attenuation of 3-BrPA-induced necrotic cell death by Nec-1. Finally, animal studies proved that 3-BrPA exhibited significant antitumor activity in nude mice. The present study is the first demonstration of 3-BrPA-induced non-apoptotic necroptosis and ROS generation in NPC cells and provides potential strategies for developing agents against apoptosis-resistant cancers.

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Section: Discussionmentioning

confidence: 99%

Inhibitory effects of 3-bromopyruvate in human nasopharyngeal carcinoma cells

et al. 2015

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“…We showed that satellite cells are induced into activity following exposure of 3-BP a potent inhibitor of glycolysis [11]. However once they have emerged from their sub-basal position, we found that their migratory processes were attenuated.…”

Section: Discussionmentioning

confidence: 70%

“…We took advantage of the myostatin null mouse that contains much thinner ECM surrounding muscle fibers compared to that of a wild-type mouse. Secondly we exploited the availability of 3-Bromo pyruvate (3-BP) a small compound inhibitor that perturbs glycolysis [11]. Both studies reveal unexpected findings.…”

Section: Introductionmentioning

confidence: 99%

Investigating the Influence of Extracellular Matrix and Glycolytic Metabolism on Muscle Stem Cell Migration on Their Native Fiber Environment

Butera

Collins‐Hooper

Mitchell

et al. 2015

Fibers

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Abstract:The composition of the extracellular matrix (ECM) of skeletal muscle fibers is a unique environment that supports the regenerative capacity of satellite cells; the resident stem cell population. The impact of environment has great bearing on key properties permitting satellite cells to carry out tissue repair. In this study, we have investigated the influence of the ECM and glycolytic metabolism on satellite cell emergence and migration-two early processes required for muscle repair. Our results show that both influence the rate at which satellite cells emerge from the sub-basal lamina position and their rate of migration. These studies highlight the necessity of performing analysis of satellite behavior on their native substrate and will inform on the production of artificial scaffolds intended for medical uses.

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“…In order to obtain more information on the mechanism of action of DIOS, enzyme inhibitors were applied: sodium fluoride (NaF) is a known inhibitor of enolase enzyme therefore it obstructs glycolysis, 3-bromopyruvic acid (3-BP) inhibits both hexokinase and pyruvate dehydrogenase enzymes [30,31], finally oligomycin A (OmA) inhibits the F O part of ATP synthase. Cells were treated with 10 lM DIOS in the absence and in the presence of different enzyme inhibitors for 12 h using the previously described conditions (Section 2.3.…”

Section: Investigation With Enzyme Inhibitorsmentioning

confidence: 99%

Flavonoid diosmetin increases ATP levels in kidney cells and relieves ATP depleting effect of ochratoxin A

Poór

Veres

Jakus

et al. 2014

Journal of Photochemistry and Photobiology B: Biology

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a b s t r a c tDiosmetin (DIOS) is a flavone aglycone commonly occurring in citrus species and olive leaves, in addition it is one of the active ingredients of some medications. Based on both in vitro and in vivo studies several beneficial effects are attributed to DIOS but the biochemical background of its action seems to be complex and it has not been completely explored yet. Previous investigations suggest that most of the flavonoid aglycones have negative effect on ATP synthesis in a dose dependent manner. In our study 17 flavonoids were tested and interestingly DIOS caused a significant elevation of intracellular ATP levels after 6-and 12-h incubation in MDCK kidney cells. In order to understand the mechanism of action, intracellular ATP and protein levels, ATP/ADP ratio, cell viability and ROS levels were determined after DIOS treatment. In addition, impacts of different enzyme inhibitors and effect of DIOS on isolated rat liver mitochondria were also tested. Finally, the influence of DIOS on the ATP depleting effect of the mycotoxin, ochratoxin A was also investigated. Our major conclusions are the followings: DIOS increases intracellular ATP levels both in kidney and in liver cells. Inhibition of glycolysis or citric acid cycle does not decrease the observed effect. DIOS-induced elevation of ATP levels is completely abolished by the inhibition of ATP synthase. DIOS is able to completely reverse the ATP-depleting effect of the mycotoxin, ochratoxin A. Most probably the DIOS-induced impact on ATP system does not originate from the antioxidant property of DIOS. Based on our findings DIOS may be promising agent to positively influence ATP depletion caused by some metabolic poisons.

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3-bromopyruvate: Targets and outcomes

Cited by 130 publications

References 74 publications

Inhibitory effects of 3-bromopyruvate in human nasopharyngeal carcinoma cells

Inhibitory effects of 3-bromopyruvate in human nasopharyngeal carcinoma cells

Investigating the Influence of Extracellular Matrix and Glycolytic Metabolism on Muscle Stem Cell Migration on Their Native Fiber Environment

Flavonoid diosmetin increases ATP levels in kidney cells and relieves ATP depleting effect of ochratoxin A

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