(05) Acetylcholinesterase biogenesis is impaired in lung cancer tissues

Martínez-Moreno, Pedro; Nieto, Susana; Ruíz-Espejo, Francisco; Torres-Lanzas, Juan; Tovar-Zapata, Isabel; Martı́nez-Hernández, Pedro; Vidal, Cecilio J.; Cabezas‐Herrera, Juan

doi:10.1016/j.cbi.2005.10.050

Cited by 10 publications

(13 citation statements)

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“…Significantly different levels of AChE activity were detected in bronchial aspirates from patients diagnosed with SCLC, AC and SCC (Table 2B). We have reported previously that AChE activity varied according to the histological classification of lung tumours [12]. In accordance with these previous findings, AChE activity in ASF from …”

Section: Ache Activity In Asf From Patients Without and With Cancersupporting

confidence: 89%

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Cancer-associated differences in acetylcholinesterase activity in bronchial aspirates from patients with lung cancer

et al. 2008

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In non-neuronal contexts, ACh (acetylcholine) is thought to be involved in the regulation of vital cell functions, such as proliferation, differentiation, apoptosis and cell-cell interaction. In airways, most cells express the non-neuronal cholinergic system, each containing a specific set of components required for synthesis, signal transduction and ACh hydrolysis. The aim of the present study was determine the expression of cholinergic system components in bronchial aspirates from control subjects and patients with lung cancer. We conducted an analysis of cholinergic components in the stored soluble and cellular fraction of bronchial aspirates from non-cancerous patients and patients diagnosed with lung cancer. The results show that the fluid secreted by human lung cells contains enough AChE (acetylcholinesterase) activity to control ACh levels. Thus these findings demonstrate that: (i) AChE activity is significantly lower in aspirates from squamous cell carcinomas; (ii) the molecular distribution of AChE in both bronchial cells and fluids consisted of amphiphilic monomers and dimers; and (iii) choline acetyltransferase, nicotinic receptors and cholinesterases are expressed in cultured human lung cells, as demonstrated by RT-PCR (reverse transcriptase-PCR). It appears that the non-neuronal cholinergic system is involved in lung physiology and lung cancer. The physiological consequences of the presence of non-neuronal ACh will depend on the particular cholinergic signalling network in each cell type. Clarifying the pathophysiological actions of ACh remains an essential task and warrants further investigation.

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Section: Ache Activity In Asf From Patients Without and With Cancersupporting

confidence: 89%

“…the synthesizing enzyme ChAT (choline acetyltransferase) [3][4][5], nAChR and mAChR (nicotinic and muscarinic ACh receptors respectively) [6][7][8][9][10][11], as well as enzymes for ACh hydrolysis AChE (acetylcholinesterase) and BChE (butyrylcholinesterase) [12,13].…”

Section: Introductionmentioning

confidence: 99%

Cancer-associated differences in acetylcholinesterase activity in bronchial aspirates from patients with lung cancer

et al. 2008

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“…The mean AChE activity in the healthy lung was shown earlier to be 10.95 ± 6.90 mU/mg 67,77 . Since the increase in the levels of AChE was found in the media (Fig.…”

Section: Resultsmentioning

confidence: 79%

IGFBP-3 Blocks Hyaluronan-CD44 Signaling, Leading to Increased Acetylcholinesterase Levels in A549 Cell Media and Apoptosis in a p53-Dependent Manner

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Muterspaugh

Clegg

et al. 2020

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105

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Insulin-like growth factor binding protein-3 (IGFBP-3) belongs to a family of six IGF binding proteins. We previously found that IGFBP-3 exerts its cytotoxic effects on A549 (p53 wild-type) cell survival through a mechanism that depends on hyaluronan-CD44 interactions. To shed light on the mechanism employed, we used CD44-negative normal human lung cells (HFL1), A549, and H1299 (p53-null) lung cancer cells. A synthetic IGFBP-3 peptide ( 215 -KKGfYKKKQcRpSKGRKR-232 ) but not the mutant (K228AR230A), was able to bind hyaluronan more efficiently than the analogous sequences from the other IGFBPs. In a manner comparable to that of the IGFBP-3 protein, the peptide blocked hyaluronan-CD44 signaling, and more effectively inhibited viability of A549 cells than viability of either H1299 or HFL1 cell lines. Treatment with the IGFBP-3 protein or its peptide resulted in increased acetylcholinesterase concentration and activity in the A549 cell media but not in the media of either HFL1 or H1299, an effect that correlated with increased apoptosis and decreased cell viability. These effects were diminished upon the same treatment of A549 cells transfected with either p53 siRNA or acetylcholinesterase siRNA. Taken together, our results show that IGFBP-3 or its peptide blocks hyaluronan-CD44 signaling via a mechanism that depends on both p53 and acetylcholinesterase.Lung cancer is a devastating human disease and among the most common causes of cancer deaths worldwide 1,2 . Of all cases of the disease, non-small cell lung cancer (NSCLC) accounts for approximately 85% 3 .CD44 is a type 1 transmembrane cell-surface glycoprotein with tumor promoting functions in many types of cancer cells 4-7 . It is the main cell surface receptor for hyaluronan (HA) 5-9 . Found on the extracellular side of the cell membrane is the CD44 globular HA-binding domain (HABD) 9,10 shown previously to bind HA as a globular water-soluble protein 11 . CD44 is encoded by a single gene 5,6,12 and many different variant isoforms (CD44v) are generated by alternative splicing that yield different patterns of amino acid insertion into the stalk domain of CD44 with the smallest being the standard CD44 (CD44s) 5,13-15 . Residues 32-123 in the N-terminal domain of CD44, common to both CD44s and CD44v isoforms, contain the HA-binding motif 16 . Assessment of CD44 expression in human lung cancer cell lines 17 , including A549 and H1299 used in this study, showed that the predominant isoform expressed is CD44s 18 . Being a common marker for tumor-initiating cells/cancer stem cells in human carcinomas, CD44 has gained much attention in the cancer literature 14 . HA-CD44 binding is known to modulate numerous downstream signaling cascades, such as the ERK1/2/MAPK and PI3K/Akt pathways, leading to tumor cell proliferation, survival, chemoresistance, and invasiveness 5,7,12,19 .HA is a non-sulfated, anionic glycosaminoglycan 5,16,20,21 polymer composed of the disaccharide sequence (D-glucuronic acid and D-N-acetylglucosamine) without known post-synthetic modification 6,22-24 ...

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“…[6] Anti-inflammatory drugs reduce the dermal, respiratory, and ocular damage caused by exposure to SM. [7] Amifostine, a radio-protective agent and its analogs have shown protection against SM toxicity in vivo and in vitro . [811] These compounds may have numerous mechanisms by which they may be imparting protection against SM.…”

Section: Introductionmentioning

confidence: 99%

Analgesic and anti-inflammatory activity of amifostine, DRDE-07, and their analogs, in mice

2010

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Objectives:To find out the analgesic and anti-inflammatory activity, if any, of Amifostine [S-2(3 amino propyl amino) ethyl phosphorothioate], DRDE-07 [S-2(3 amino ethyl amino) ethyl phenyl sulphide] and their analogs DRDE-30 and DRDE-35, the probable prophylactic agent for sulphur mustard (SM).Materials and Methods:In order to find out the analgesic activities of the compounds two methods were employed, namely, acetic acid-induced writhing test and formalin-induced paw licking. The persistent pain model of formalin-induced hind paw licking was carried out to test the effect of the compounds on neurogenic pain or early phase (0 to 5 minutes) and on the peripheral pain or the late phase (15 to 30 minutes). To test the effect of the compound in acute inflammation, carrageenan-induced hind paw edema was carried out. This model of inflammation involves a variety of mediators of inflammation.Results:DRDE-07 (81.7%) and DRDE-30 (79.4%) showed significant reduction in the acetic acid-induced writhing test. DRDE-07 (93.1%), DRDE-30 (82%), and DRDE-35 (61.3%) showed significant reduction in the second or late phase of formalin-induced paw licking. All the analogs (more than 60%) including amifostine (43.9%) showed significant reduction of paw edema in the carrageenan-induced paw edema in mice.Conclusion:The analgesic and anti-inflammatory activity of the antidotes were comparable with aspirin.

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(05) Acetylcholinesterase biogenesis is impaired in lung cancer tissues

Cited by 10 publications

References 5 publications

Cancer-associated differences in acetylcholinesterase activity in bronchial aspirates from patients with lung cancer

Cancer-associated differences in acetylcholinesterase activity in bronchial aspirates from patients with lung cancer

IGFBP-3 Blocks Hyaluronan-CD44 Signaling, Leading to Increased Acetylcholinesterase Levels in A549 Cell Media and Apoptosis in a p53-Dependent Manner

Analgesic and anti-inflammatory activity of amifostine, DRDE-07, and their analogs, in mice

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