Investigating Effects of Acidic pH on Proliferation, Invasion and Drug-Induced Apoptosis in Lymphoblastic Leukemia

Bohloli, Mahbobeh; Atashi, Amir; Soleimani, Masoud; Kaviani, Saeid; Anbarlou, Azadeh

doi:10.1007/s12307-016-0187-0

Cited by 26 publications

(14 citation statements)

References 35 publications

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“…It has been shown that extracellular pH of cancer cells is slightly acidic (pH 6.2–6.9) than that of normal cells (pH 7.2–7.5). Acidic environment not only promotes cancer cell transcription of tumor-promoting factors such as VEGF, IL-8 and hypoxia-inducible factor (HIF-1) [ 262 – 264 ], but increases the expression of proteases like MMPs and cathepsins that facilitate migration of the cancer cells [ 265 ].…”

Section: Introductionmentioning

confidence: 99%

Native-mimicking in vitro microenvironment: an elusive and seductive future for tumor modeling and tissue engineering

Rijal

2018

J Biol Eng

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Human connective tissues are complex physiological microenvironments favorable for optimal survival, function, growth, proliferation, differentiation, migration, and death of tissue cells. Mimicking native tissue microenvironment using various three-dimensional (3D) tissue culture systems in vitro has been explored for decades, with great advances being achieved recently at material, design and application levels. These achievements are based on improved understandings about the functionalities of various tissue cells, the biocompatibility and biodegradability of scaffolding materials, the biologically functional factors within native tissues, and the pathophysiological conditions of native tissue microenvironments. Here we discuss these continuously evolving physical aspects of tissue microenvironment important for human disease modeling, with a focus on tumors, as well as for tissue repair and regeneration. The combined information about human tissue spaces reflects the necessities of considerations when configuring spatial microenvironments in vitro with native fidelity to culture cells and regenerate tissues that are beyond the formats of 2D and 3D cultures. It is important to associate tissue-specific cells with specific tissues and microenvironments therein for a better understanding of human biology and disease conditions and for the development of novel approaches to treat human diseases.

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Section: Introductionmentioning

confidence: 99%

Native-mimicking in vitro microenvironment: an elusive and seductive future for tumor modeling and tissue engineering

Rijal

2018

J Biol Eng

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“…8 Other studies have shown that the extracellular acid environment can reduce the apoptotic potential, change the genetic properties, and increase the activity of multidrug transporters to make tumor cells resistant to drug resistance, thereby evading the damage of chemotherapy drugs. 9,10 In addition, studies have shown that the extracellular acid environment can increase the expression of interleukin 8 (IL-8), vascular endothelial growth factor (VEGF), cathepsin B (CTSB), matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9). 11,12 In short, the extracellular low-acid environment contributes to chemotherapy resistance, but the molecular mechanism is still unclear.…”

Section: Intruductoinmentioning

confidence: 99%

ASIC1a Stimulates the Resistance of Human Hepatocellular Carcinoma by Promoting Epithelial-mesenchymal Transition via the AKT/GSK3β/Snail Signaling Pathway

Zhang

Cao

Gao

et al. 2021

Preprint

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Background: The main obstacle to the cure of hepatocellular carcinoma (HCC) is multidrug resistance. Acid sensing ion channel 1a (ASIC1a) acts as a critical roles in all stages of cancer progression, especially invasion and metastasis as well as in resistance to therapy. Epithelial to mesenchymal transition (EMT) is a phenomenon in which epithelial cells transform into mesenchymal cells after being stimulated by extracellular factors and is closely related to tumor infiltration and resistance. Methods: Western blotting assay, Immunofluorescence (IF) staining, Immunohistochemistry (IHC) staining, MTT and colony formation assay and scratch healing assay were used to detect the level of ASIC1a and the cell proliferation, migration and invasion capabilities in this research.Results: In this research, we found that the protein of ASIC1a is overexpressed in HCC cancer tissues. In addition, we identified that the levels of ASIC1a are highly expressed in resistant HCC cells. Compared with the parental cells, EMT occurred more frequently in drug-resistant cells. Functional studies demonstrated that inactivation of ASIC1a restrained cell migration and invasion and enhanced the chemosensitivity of cells through EMT. In HCC cells, the overexpression of ASIC1a stimulates the up-regulation of EMT characterization molecular level and proliferation, migration and invasion capabilities and further induces drug resistance, while knocking down ASIC1a with short hairpin RNA (shRNA) has the opposite effect. Further investigations found that ASIC1a increased cell migration and invasion through EMT by regulating α and β-catenin, vimentin and fibronectin expression via AKT/GSK-3β/Snail pathway. Conclusions: Our study demonstrated that ASIC1a acts an important assignment in drug resistance of HCC through EMT via AKT/GSK-3β/Snail pathway, thereby lending a latent therapeutic objective and new ideas regarding to HCC.

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“…While several studies have demonstrated that a low extracellular pH favors the induction of apoptosis (Ding et al, 2000;Thatte et al, 2004;Kumar et al, 2007), in other studies acidification has been found to inhibit apoptosis. A protective effect of acidosis has been observed in different cell types including endothelial cells (D'Arcangelo et al, 2000;D'Arcangelo et al, 2002;Terminella et al, 2002;Kumar et al, 2008), liver cells (Currin et al, 1991), lymphoblastic cells (Bohloli et al, 2016), neurons (Xu et al, 1998), colon adenocarcinoma cells (Sharma et al, 2005) and osteoclasts (Pereverzev et al, 2008). The mechanisms underlying the protective effect of acidosis against apoptosis are still unclear.…”

Section: Introductionmentioning

confidence: 99%

Low pH Attenuates Apoptosis by Suppressing the Volume-Sensitive Outwardly Rectifying (VSOR) Chloride Current in Chondrocytes

Kittl

Winklmayr

Preishuber-Pflügl

et al. 2022

Front. Cell Dev. Biol.

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In a variety of physiological and pathophysiological conditions, cells are exposed to acidic environments. Severe synovial fluid acidification also occurs in a progressive state of osteoarthritis (OA) affecting articular chondrocytes. In prior studies extracellular acidification has been shown to protect cells from apoptosis but the underlying mechanisms remain elusive. In the present study, we demonstrate that the inhibition of Cl− currents plays a significant role in the antiapoptotic effect of acidification in human articular chondrocytes. Drug-induced apoptosis was analyzed after exposure to staurosporine by caspase 3/7 activity and by annexin-V/7-actinomycin D (7-AAD) staining, followed by flow cytometry. Cell viability was assessed by resazurin, CellTiter-Glo and CellTiter-Fluor assays. Cl− currents and the mean cell volume were determined using the whole cell patch clamp technique and the Coulter method, respectively. The results reveal that in C28/I2 cells extracellular acidification decreases caspase 3/7 activity, enhances cell viability following staurosporine treatment and gradually deactivates the volume-sensitive outwardly rectifying (VSOR) Cl− current. Furthermore, the regulatory volume decrease (RVD) as well as the apoptotic volume decrease (ADV), which represents an early event during apoptosis, were absent under acidic conditions after hypotonicity-induced cell swelling and staurosporine-induced apoptosis, respectively. Like acidosis, the VSOR Cl− current inhibitor DIDS rescued chondrocytes from apoptotic cell death and suppressed AVD after induction of apoptosis with staurosporine. Similar to acidosis and DIDS, the VSOR channel blockers NPPB, niflumic acid (NFA) and DCPIB attenuated the staurosporine-induced AVD. NPPB and NFA also suppressed staurosporine-induced caspase 3/7 activation, while DCPIB and Tamoxifen showed cytotoxic effects per se. From these data, we conclude that the deactivation of VSOR Cl− currents impairs cell volume regulation under acidic conditions, which is likely to play an important role in the survivability of human articular chondrocytes.

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Investigating Effects of Acidic pH on Proliferation, Invasion and Drug-Induced Apoptosis in Lymphoblastic Leukemia

Cited by 26 publications

References 35 publications

Native-mimicking in vitro microenvironment: an elusive and seductive future for tumor modeling and tissue engineering

Native-mimicking in vitro microenvironment: an elusive and seductive future for tumor modeling and tissue engineering

ASIC1a Stimulates the Resistance of Human Hepatocellular Carcinoma by Promoting Epithelial-mesenchymal Transition via the AKT/GSK3β/Snail Signaling Pathway

Low pH Attenuates Apoptosis by Suppressing the Volume-Sensitive Outwardly Rectifying (VSOR) Chloride Current in Chondrocytes

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