The role of intracellular pathways in the proliferation of human K562 cells mediated by muscarinic receptors

Aydın, Banu; Kan, Beki; Cabadak, Hülya

doi:10.1016/j.leukres.2013.05.018

Cited by 13 publications

(12 citation statements)

References 45 publications

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“…Acetylcholine serves as a neurotransmitter both in the central and the peripheral nervous systems, where it controls functions including muscle contraction, neurotransmission among others. Recent studies demonstrating that ACh also regulates cell proliferation [19] and apoptosis [20] initiated research on the role of nAChRs and mAChRs in the development and progression of cancer and in stem cell physiology. Based on these studies, we asked whether the M 3 R subtype may affect the proliferation of the K562 cell line.…”

Section: Discussionmentioning

confidence: 99%

Effects of carbachol on apoptosis in human chronic myelogenous leukemic K562 cell line

Aydın¹,

Tulunay²,

Kan³

et al. 2019

Marmara Medical Journal

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Objectives: Muscarinic receptors mediate diverse actions of acetylcholine in the central nervous system and in non-nervous tissues innervated by the parasympathetic nervous system. Our study aims to evaluate the potential association of the M 3 muscarinic receptor with K562 cell proliferation and death. Materials and Methods: Cell proliferation was evaluated by bromodeoxyuridine (BrDU) incorporation. To show early, late apoptosis and cell death, cells were labelled with Annexin V, propidium iodide (PI) and analyzed by flow cytometry. Nuclear extracellular signal-regulated kinase (ERK/pERK) expression was measured by western blot analysis. Results: Treatment with carbachol (CCh) for 48h decreased cell number. Exposing K562 cells to CCh for 24h decreased the number of early apoptotic cells but did not change the number of late apoptotic and necrotic cells. CCh treatment for 48h increased the number of necrotic cells, but decreased the number of early and late apoptotic cells. In response to CCh, nuclear ERK expression was increased and this effect was reversed by 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide (4DAMP). Nuclear pERK expression was decreased in CCh treated cells, 4DAMP did not reverse the effect. Conclusion: Our data suggest that cholinergic agonist CCh affects cell proliferation in K562 cells not only through muscarinic receptors but also through other cholinergic receptors.

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Section: Discussionmentioning

confidence: 99%

Effects of carbachol on apoptosis in human chronic myelogenous leukemic K562 cell line

Aydın¹,

Tulunay²,

Kan³

et al. 2019

Marmara Medical Journal

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“…Collectively, these observations support the association of M3-mAChR in myeloid maturation. It is notable that in previous studies of the CML K562 cell line, muscarinic receptor activation stimulated intracellular cAMP, decreased c-Fos and cyclin D1 expression, and inhibited cell proliferation (19,23). Altogether, mAChR activation by its agonist may also be a potential approach for treatment of CML.…”

Section: Discussionmentioning

confidence: 91%

Variation of nicotinic subtype α7 and muscarinic subtype M3 acetylcholine receptor expression in three main types of leukemia

et al. 2018

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Cholinergic receptors, such as α7-nicotinic acetylcholine receptor (α7-nAChR) and M3-muscarinic acetylcholine receptor (M3-mAChR), have been demonstrated to serve a significant role in the proliferation, differentiation and apoptosis of leukemic cells. However, the expression of these receptors in samples from patients with leukemia remains unclear. The present study aimed to determine the expression of M3-mAChR and α7-nAChR in the bone marrow or peripheral blood of 51 patients with leukemia, including acute myeloid leukemia (AML; n=33), acute lymphoblastic leukemia (ALL; n=13), and chronic myeloid leukemia (CML; n=5). Peripheral blood mononuclear cells (PBMCs) were also isolated from healthy subjects (n=5) for comparison. Western blot analysis was performed to determine the protein expression profiles, and a pattern of decreased α7-nAChR levels in patients with leukemia was observed. Among the leukemia types, the lowest expression of α7-nAChR and M3-mAChR were identified in patients with T-cell ALL/lymphoma (T-ALL). CML exhibited the highest level of M3-mAChR, which was significantly different from APL and AML-M4, yet not from healthy subjects (P<0.05). Therefore, different expression profiles of α7-nACR and M3-mAChR were detected amongst the leukemia types. Collectively, the present study supports the potential role of cholinergic signaling in mediating leukemogenesis. However, further studies in larger cohorts are required to validate these findings.

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“…The treatment of serum-deprived human erythroleukemia K562 cells with carbachol (CCh), a cholinergic agonist, led to a significant increase in DNA synthesis. CCh, also could produce a decrease in the DNA synthesis in human erythroleukemia K562 cells supplemented with 1% or 10% FBS after starvation [9]. The results of our previous studies also showed that nitric oxide (NO) release increased through M 3 receptors in the human erythroleukemia K562 cells [7].…”

Section: Introductionmentioning

confidence: 77%

“…The protein content of the whole lysates was determined by the method of Lowry et al [15]. Immunoblot analyses were described in our previous studies with minor modification [9]. 100 mg of protein was used in immunoblots and blots incubated overnight at 4°C with antibodies against caspase 3, 8, 9 and b-actin in separate blots.…”

Section: Preparation Of Whole-cell Lysates and Immunoblot Analysismentioning

confidence: 99%

“…Muscarinic receptor subtypes have different functions [5]. In our previous studies we showed that M 2 , M 3 and M 4 subtypes of mAChR were expressed in human erythroleukemia K562 cell line and muscarinic activation led to erythroleukemia cell proliferation dependent on the presence of fetal bovine serum (FBS) [7][8][9]. The treatment of serum-deprived human erythroleukemia K562 cells with carbachol (CCh), a cholinergic agonist, led to a significant increase in DNA synthesis.…”

Section: Introductionmentioning

confidence: 99%

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Effects of cholinergic compounds and TNF-alpha on human erythroleukemia K562 cell proliferation and caspase expression

Kanli¹,

Aydın²,

Cabadak³

2019

Marmara Medical Journal

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Objective: The purpose of this study was to investigate if stimulating auto-paracrine muscarinic receptor signalling pathway could change human erythroleukemia K562 cell proliferation and caspase 3, 8 and 9 expression levels. To better understand the role of muscarinic receptors in cell signalling mechanism, we investigated the effects of several compounds on human erythroleukemia K562 cell proliferation and caspase 3, 8 and 9 expression. These compounds were M 3 muscarinic receptor agonist, pilocarpine, proinflammatory cytokine, tumor necrosis factor (TNF)-alpha, and the wortmannin which is a phosphoinositide 3-kinase inhibitor.Materials and Methods: Cell proliferation and cell viability were evaluated by the trypan blue exclusion test and 5-Bromo-2deoxy-uridine (BrdU) Labelling and Detection Kits. Caspase 3, 8 and 9 expression levels were determined by immunoblot analysis.Results: Both pilocarpine and TNF-alpha caused a small increase in human erythroleukemia K562 cell proliferation. However, when all the compounds were treated together, proliferation of human erythroleukemia K562 cells increased significantly when compared to untreated control cells. TNF-alpha and wortmannin treatment increased caspase 3 and caspase 8 expression patterns significantly in human erythroleukemia K562 cells. TNF-alpha and wortmannin treatment increased caspase 9 expression level (P>0.05) but it was not significant.Conclusion: These findings partly demonstrated that M 3 muscarinic receptor mediated an increase in K562 cell proliferation. Pilocarpine prevented TNF-alpha and wortmannin induced caspase 3 and 8 expression and indirectly showed apoptosis in human erythroleukemia K562 cells.

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The role of intracellular pathways in the proliferation of human K562 cells mediated by muscarinic receptors

Cited by 13 publications

References 45 publications

Effects of carbachol on apoptosis in human chronic myelogenous leukemic K562 cell line

Effects of carbachol on apoptosis in human chronic myelogenous leukemic K562 cell line

Variation of nicotinic subtype α7 and muscarinic subtype M3 acetylcholine receptor expression in three main types of leukemia

Effects of cholinergic compounds and TNF-alpha on human erythroleukemia K562 cell proliferation and caspase expression

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