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

Suriyo, Tawit; Chotirat, Sadudee; Auewarakul, Chirayu; Chaiyot, Karnjana; Promsuwicha, Orathai; Satayavivad, Jutamaad

doi:10.3892/ol.2018.9663

Cited by 4 publications

(4 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Primary CLL cells express α7-nAChR at a higher level than normal B-cells, and inhibiting α7-nAChRs in a range of leukemic cell lines reduces cell migration ( 151 ). Conversely, protein expression levels of α7-nAChRs in AML, CML and ALL patient peripheral blood or bone marrow-derived mononuclear cells was lower than in healthy subjects ( 178 ). Acetylcholine causes an increase in intracellular Ca 2+ levels in CML-derived K-562 cells, and the α7-nAChR antagonist methyllycaconitine citrate inhibits K-562 cell proliferation as well as reduces the intracellular Ca 2+ levels ( 177 ).…”

Section: Calcium Signaling Deregulation In Blood Cancermentioning

confidence: 99%

Deregulated calcium signaling in blood cancer: Underlying mechanisms and therapeutic potential

Immanuel

Li²,

Green³

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

Intracellular calcium signaling regulates diverse physiological and pathological processes. In solid tumors, changes to calcium channels and effectors via mutations or changes in expression affect all cancer hallmarks. Such changes often disrupt transport of calcium ions (Ca2+) in the endoplasmic reticulum (ER) or mitochondria, impacting apoptosis. Evidence rapidly accumulates that this is similar in blood cancer. Principles of intracellular Ca2+ signaling are outlined in the introduction. We describe different Ca2+-toolkit components and summarize the unique relationship between extracellular Ca2+ in the endosteal niche and hematopoietic stem cells. The foundational data on Ca2+ homeostasis in red blood cells is discussed, with the demonstration of changes in red blood cell disorders. This leads to the role of Ca2+ in neoplastic erythropoiesis. Then we expand onto the neoplastic impact of deregulated plasma membrane Ca2+ channels, ER Ca2+ channels, Ca2+ pumps and exchangers, as well as Ca2+ sensor and effector proteins across all types of hematologic neoplasms. This includes an overview of genetic variants in the Ca2+-toolkit encoding genes in lymphoid and myeloid cancers as recorded in publically available cancer databases. The data we compiled demonstrate that multiple Ca2+ homeostatic mechanisms and Ca2+ responsive pathways are altered in hematologic cancers. Some of these alterations may have genetic basis but this requires further investigation. Most changes in the Ca2+-toolkit do not appear to define/associate with specific disease entities but may influence disease grade, prognosis, treatment response, and certain complications. Further elucidation of the underlying mechanisms may lead to novel treatments, with the aim to tailor drugs to different patterns of deregulation. To our knowledge this is the first review of its type in the published literature. We hope that the evidence we compiled increases awareness of the calcium signaling deregulation in hematologic neoplasms and triggers more clinical studies to help advance this field.

show abstract

Section: Calcium Signaling Deregulation In Blood Cancermentioning

confidence: 99%

Deregulated calcium signaling in blood cancer: Underlying mechanisms and therapeutic potential

Immanuel

Li²,

Green³

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…CEM cells also express functional mAChRs linked to NO synthesis by nNOS and/or iNOS [28]. Also, both mAChRs and nAChRs were described in T-ALL primary cells [66], suggesting that these cells can also respond to ACh or ACh agonists.…”

Section: Ach and Cholinergic Receptorsmentioning

confidence: 99%

“…The analysis of signaling pathways following low or high doses of S1P suggests that Rac1 activity is possibly involved in regulating these specific migratory responses [38]. Moreover, using a T-LBL model in zebrafish, a study has shown that the inhibition of S1P1 induces lymphoma cells to disaggregate and intravasate into the vasculature in vivo, thus implicating high S1P1 levels in the blockade of T-LBL dissemination [81].…”

Section: Other Molecular Circuits Possibly Related To Thymus-brain Co...mentioning

confidence: 99%

Thymus-brain connections in T-cell Acute Lymphoblastic Leukemia

Mendes-da-Cruz,

Belorio,

Cotta-de-Almeida

2024

Neuroimmunomodulation

View full text Add to dashboard Cite

Background: T-cell acute lymphoblastic leukemia (T-ALL) is a malignant hematologic disease caused by the transformation and uncontrolled proliferation of T-cell precursors. T-ALL is generally thought to originate in the thymus since lymphoblasts express phenotypic markers comparable to those described in thymocytes in distinct stages of development. Although around 50% of T-ALL patients present a thymic mass, T-ALL is characterized by peripheral blood and bone marrow involvement, and central nervous system (CNS) infiltration is one of the most severe complications of the disease. Summary: The CNS invasion is related to the expression of specific adhesion molecules and receptors commonly expressed in developing T cells, such as L-selectin, CD44, integrins, and chemokine receptors. Furthermore, T-ALL blasts also express neurotransmitters, neuropeptides and cognate receptors that are usually present in the CNS and can affect both the brain and thymus, participating in the crosstalk between the organs. Key messages: This review discusses how the thymus-brain connections, mediated by innervation and common molecules and receptors, can impact the development and migration of T-ALL blasts, including CNS infiltration.

show abstract

“…Additionally, in human glioblastoma, the M2-mAChR agonist arecaidine inhibited cell proliferation and survival in cancer stem cells [ 15 ]. It was also reported that cholinergic receptors M3-mAChR play a significant role in the proliferation, differentiation, and apoptosis of leukemia cells [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

In Vitro Characterization of Inhibitors for Lung A549 and Leukemia K562 Cell Lines from Fungal Transformation of Arecoline Supported by In Silico Docking to M3-mAChR and ADME Prediction

et al. 2022

View full text Add to dashboard Cite

The search for anticancer drugs is of continuous interest. Arecoline is an alkaloid with anticancer activity. Herein, the metabolism of arecoline through fungal transformation was investigated for the discovery of potential anticancer drugs with higher activity and selectivity. Compounds 1–5 were isolated, and their structures were fully elucidated using various spectroscopic analyses, including 1D and 2D NMR, ESIMS, and HRESIMS. This is the first report for the isolation of compounds 1 and 2. An MTT assay was performed to determine the cytotoxic activity of arecoline and its metabolites in vitro using non-small-cell lung cancer A549 and leukemia K562 cell lines compared to staurosporine and doxorubicin as positive controls. For the non-small-cell lung A549 cell line, arecoline hydrobromide, staurosporine, and doxorubicin resulted in IC50 values of 11.73 ± 0.71 µM, 10.47 ± 0.64 µM, and 5.05 ± 0.13 µM, respectively, while compounds 1, 3, and 5 exhibited IC50 values of 3.08 ± 0.19 µM, 7.33 ± 0.45 µM, and 3.29 ± 0.20 µM, respectively. For the leukemia K562 cell line, the IC50 values of arecoline hydrobromide, staurosporine, and doxorubicin were 15.3 ± 1.08 µM, 5.07 ± 0.36 µM, and 6.94 ± 0.21 µM, respectively, while the IC50 values of compounds 1, 3 and 5 were 1.56 ± 0.11 µM, 3.33 ± 0.24 µM, and 2.15 ± 0.15 µM, respectively. The selectivity index value of these compounds was higher than 3. These results indicated that compounds 1, 3, and 5 are very strong cytotoxic agents with higher activity than the positive controls and good selectivity toward the tested cancer cell lines. Cell cycle arrest was then studied by flow cytometry to investigate the apoptotic mechanism. Docking simulation revealed that most compounds possessed good binding poses and favorable protein-ligand interactions with muscarinic acetylcholine receptor M3-mAChR protein. In silico study of pharmacokinetics using SwissADME predicted compounds 1–5 to be drug-like with a high probability of good oral bioavailability.

show abstract

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

Cited by 4 publications

References 25 publications

Deregulated calcium signaling in blood cancer: Underlying mechanisms and therapeutic potential

Deregulated calcium signaling in blood cancer: Underlying mechanisms and therapeutic potential

Thymus-brain connections in T-cell Acute Lymphoblastic Leukemia

In Vitro Characterization of Inhibitors for Lung A549 and Leukemia K562 Cell Lines from Fungal Transformation of Arecoline Supported by In Silico Docking to M3-mAChR and ADME Prediction

Contact Info

Product

Resources

About