Acetylcholinesterase and butyrylcholinesterase histochemical activities and tumor cell growth in several brain tumors

Barbosa, Milton; Rios, Oscar; Velásquez, Miguel A.; Villalobos, Julio; Ehrmanns, Jorge

doi:10.1016/s0090-3019(01)00351-2

Cited by 22 publications

(14 citation statements)

References 40 publications

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“…Among the examined molecules, only ACHE, the Ach hydrolytic enzyme, was obviously down‐regulated in almost 70% of detected cancer tissues from 240 HCC patients. Despite much evidence suggesting the abnormal expression of the ACHE gene in various tumor types,9 no causal relationship has been established between the ACHE expression level and tumor development, except in the case of astrocytoma 15. An ACHE‐derived peptide displayed growth factor activity in hematopoiesis,16 and a role of ACHE as a myeloid tumor suppressor gene has been postulated 17.…”

Section: Discussionmentioning

confidence: 99%

Acetylcholinesterase, a key prognostic predictor for hepatocellular carcinoma, suppresses cell growth and induces chemosensitization

Zhao

Wang

et al. 2011

Hepatology

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Acetylcholinesterase (ACHE) plays important roles in the cholinergic system, and its dysregulation is involved in a variety of human diseases. However, the roles and implications of ACHE in hepatocellular carcinoma (HCC) remain elusive. Here we demonstrate that ACHE was significantly down-regulated in the cancerous tissues of 69.2% of HCC patients, and the low ACHE expression in HCC was correlated with tumor aggressiveness, an elevated risk of postoperative recurrence, and a low survival rate. Both the recombinant ACHE protein and the enhanced expression of ACHE significantly inhibited HCC cell growth in vitro and tumorigenicity in vivo. Further study showed that ACHE suppressed cell proliferation via its enzymatic activity of acetylcholine catalysis and degradation. Moreover, ACHE could inactivate mitogenactivated protein kinase and phosphatidyl inositol-3 0 -phosphate kinase/protein kinase B pathways in HCC cells and thereby increase the activation of glycogen synthase kinase 3b and lead to b-catenin degradation and cyclin D1 suppression. In addition, increased ACHE expression could remarkably sensitize HCC cells to chemotherapeutic drugs (i.e., adriamycin and etoposide). Conclusion: For the first time, we describe the function of ACHE as a tumor growth suppressor in regulating cell proliferation, the relevant signaling pathways, and the drug sensitivity of HCC cells. ACHE is a promising independent prognostic predictor for HCC recurrence and the survival of HCC patients. These findings provide new insights into potential strategies for drug discovery and improved HCC treatment. (HEPATOLOGY 2011;53:493-503) H epatocellular carcinoma (HCC) is one of the most prevalent human malignancies worldwide and especially in East Asia and South Africa. 1The risk factors for HCC, such as aflatoxin B exposure and hepatitis B virus or hepatitis C virus infection, are well documented. However, the molecular pathogenesis of HCC remains to be comprehensively elucidated. Making matters worse, the particularly high rate of postsurgical recurrence (50%-70% at 5 years) renders this disease a major challenge that is highly refractory to conventional chemotherapy and radiation. 2Our previous study, which was based on a largescale complementary DNA transfection screening, showed that some neurotransmitter-related genes are involved in HCC cell proliferation or survival.3 Neurotransmitters have been for a long time considered to be confined to the nervous system, and reports about the presence of neurotransmitters in microorganisms, plants, and lower animals have emerged in recent years. 4 The transmitter acetylcholine (Ach) might function in the regulation of cell fates such as proliferation, differentiation, and the establishment of cell-cell

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Section: Discussionmentioning

confidence: 99%

Acetylcholinesterase, a key prognostic predictor for hepatocellular carcinoma, suppresses cell growth and induces chemosensitization

Zhao

Wang

et al. 2011

Hepatology

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“…Benzoate esters were also synthesized, as previously described 24 , (Scheme 1, Table 1, 1-3) in order to directly compare cholinesterase kinetic parameters for aryl thioesters and esters. Two classes of thioesters were synthesized, those from aryl acid chlorides (Table 1, [4][5][6], analogous to the benzoate esters, and those from alkyl acid chlorides (Table 1, [7][8][9], analogous to previously developed alkyl ester imaging agents 17,22 .…”

Section: Organic Synthesismentioning

confidence: 99%

“…The cholinergic system is affected in a number of disorders, such as Alzheimer's disease (AD) [1][2][3] , multiple sclerosis 4,5 and primary brain tumors 6 . In the brain cholinergic system, two enzymes, acetylcholinesterase (AChE, EC 3.1.1.7) and butyrylcholinesterase (BuChE, EC 3.1.1.8), catalyze the hydrolysis of acetylcholine, thereby regulating the actions of this neurotransmitter 7 .…”

Section: Introductionmentioning

confidence: 99%

Thioesters for the in vitro evaluation of agents to image brain cholinesterases

Macdonald

Jollymore

Reid

et al. 2012

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…Both enzymes can be distinguished based on their own substrate specificities, which are acetylcholine (ACh) for AChE and butyrylcholine (BuCh) for BuChE (Principato et al, 1989;Barbosa et al, 2001;Pohanka et al, 2011;Romani et al, 2011). BuChE is also known as pseudocholinesterase as its capability to hydrolyse both ACh and BuCh at different frequencies (Forget et al, 2002;Khan et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Purification and Anticholinesterase Sensitivity of Cholinesterase Extracted from Liver Tissue of Puntius Javanicus

Sabullah¹,

Shukor²,

Shamaan³

et al. 2015

IJAB

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The purification of a soluble cholinesterase (ChE) from Puntius javanicus liver using affinity chromatography was studied. Affinity matrix was synthesised through the cooling system of ligands procainamide to epoxy-activated Sephacryl 6B and purification process was performed using calibrated flow rate at 0.2 mL/min. Non-denaturing electrophoresis condition was employed and the single band native form of ChE was detected at 66.267 kDa after being stained with commasie brilliant blue. ChE detection was performed using gel filtration; ZORBAX column attached to the HPLC with the flow rate of 1 mL/min. Only a single peak was detected at the retention time of 3.720. From the assay evaluation, the final purified ChE procedure displayed the highest sensitivity of detecting the anticholinesterase namely mercury, copper, malaoxon and carbofuran compared to the impure ChE and the results were further discussed in detail to the potential application of ChE from P. javanicus as a biomarker for those toxicants.

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Acetylcholinesterase and butyrylcholinesterase histochemical activities and tumor cell growth in several brain tumors

Cited by 22 publications

References 40 publications

Acetylcholinesterase, a key prognostic predictor for hepatocellular carcinoma, suppresses cell growth and induces chemosensitization

Acetylcholinesterase, a key prognostic predictor for hepatocellular carcinoma, suppresses cell growth and induces chemosensitization

Thioesters for the in vitro evaluation of agents to image brain cholinesterases

Purification and Anticholinesterase Sensitivity of Cholinesterase Extracted from Liver Tissue of Puntius Javanicus

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