Cytotoxicity of atropine to human corneal epithelial cells by inducing cell cycle arrest and mitochondrion-dependent apoptosis

Tian, Chenglei; Wen, Qian; Fan, Ting-Jun

doi:10.1016/j.etp.2015.07.006

Cited by 26 publications

(23 citation statements)

References 43 publications

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“…Our hypothesis on the cytotoxicity of propranolol or atropine confirms previous studies, where propranolol applied up to 200 μmol/L was found to reduce the viability of U266 human multiple myeloma cells in a dose‐dependent manner in parallel with loss of MMP and induction of cell death by apoptosis . With regard to atropine, it has been found to have considerable cytotoxic effects on human corneal epithelial cells when used at concentrations ≥0.3125 g/L (which corresponds with 1 mmol/L and approximately 3% of therapeutic dosage in eye clinic) …”

Section: Discussionsupporting

confidence: 87%

“…The cells were treated with the test chemicals, and alterations in mitochondrial membrane potential were monitored. Six of the chemicals are known to induce apoptosis (paracetamol, ethanol, propranolol, cobalt chloride, formaldehyde and atropine) and another two possess cytotoxic potential (isopropyl alcohol and glycerol) . Drugs with pro‐apoptotic activity were chosen, as the study was intended to characterize the function of mitochondria, which are known to be involved in the apoptotic signalling pathway .…”

Section: Methodsmentioning

confidence: 99%

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Differentiated mitochondrial function in mouse 3T3 fibroblasts and human epithelial or endothelial cells in response to chemical exposure

Boncler

Łukasiak²,

Dastych

et al. 2018

Basic Clin Pharma Tox

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Mouse 3T3 fibroblasts are commonly used for in vitro toxicity testing; however, their sensitivity to stimuli is not well defined. To assess the sensitivity of the 3T3 cell line, the study compared the changes in mitochondrial membrane potential (MMP) occurring after exposure to eight chemicals known to demonstrate pro-apoptotic activity (glycerol, isopropanol, ethanol, paracetamol, propranolol, cobalt chloride, formaldehyde and atropine). Five cell lines were used as follows: mouse 3T3 fibroblasts, human epithelial cells (A549, Caco-2 and HepG2) and human endothelial cells (HMEC-1). Cell sensitivity was assessed based on the total area under and over the dose-response curves (AUOC) in relation to baselines. The 3T3 fibroblasts had the highest AUOC values and were the most sensitive to the action of all the examined chemicals, with the exception of formaldehyde. Significant changes in MMP between the 3T3 cell line and other cells were observed after cell treatment with atropine (A549, Caco-2 or HMEC-1 cells vs 3T3 cells, P < 0.05), propranolol (A549 vs 3T3 cells, P < 0.01; HepG2 vs 3T3 cells, P < 0.05), cobalt chloride (A549 cells vs 3T3 cells, P < 0.01) or ethanol (HMEC-1 vs 3T3, P < 0.05). Formaldehyde appeared the most toxic compound for Caco-2 cells (Caco-2 vs 3T3 cells, P < 0.05). The surface areas (AUOC) calculated for each other chemical and obtained for HepG2, Caco-2, A549 and HMEC-1 did not differ significantly between cell lines. We postulate that mouse 3T3 fibroblasts demonstrate significantly higher relative sensitivity to many agents with toxic potential.

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Section: Discussionsupporting

confidence: 87%

Section: Methodsmentioning

confidence: 99%

Differentiated mitochondrial function in mouse 3T3 fibroblasts and human epithelial or endothelial cells in response to chemical exposure

Boncler

Łukasiak²,

Dastych

et al. 2018

Basic Clin Pharma Tox

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“…Mitochondrial pathway (42), death receptor-mediated pathway (43) and endoplasmic reticulum pathway (44) are the major signal transduction pathways that induced apoptosis (45,46), which ultimately induce cell apoptosis by activating caspase-3 (47). We found that oridonin evoked caspase-3 activation, as evidenced by the appearance of 17 kDa subunits, which showed that oridonin induced SGC-7901 apoptosis was caspase-3 dependent.…”

Section: Discussionmentioning

confidence: 74%

Oridonin induces apoptosis through the mitochondrial pathway in human gastric cancer SGC-7901 cells

Gao

Tan

Zhu

et al. 2016

International Journal of Oncology

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Abstract.Oridonin is one of the most important antitumor active ingredients of Rabdosia rubescens. Recently published studies from our laboratory have demonstrated that oridonin was able to arrest human gastric cancer SGC-7901 cells at G 2 /M phase. However, little is known about inducing apoptosis in gastric cancer. The aim of this study was to investigate the effect of oridonin on antineoplastic capability of SGC-7901 cells and the detailed molecular mechanism of oridoninmediated intrinsic pathway of apoptosis. Cell proliferation was assessed by MTT assay while apoptosis induced by oridonin was determined by Hoechst 33342 staining assay and Annexin V/PI double staining assay. Early apoptotic rate was stained by Annexin V/PI and detected by flow cytometry. Apoptosis pathway was analyzed by western blot analysis of Bcl-2, Bax, cytochrome c and caspase-3 expression. The results showed that oridonin was able to inhibit the SGC-7901 cell proliferation, the 50% growth inhibition (IC 50 ) was 22.74 µM. Oridonin could induce cell apoptosis of SGC-7901 cells and the early apoptotic rates induced by 0, 20, 40, 80 µmol/l oridonin were 1.53±0.67, 3.33±0.29, 84.80±0.82 and 96.43±0.51%, respectively. Western blot analysis revealed that oridonin downregulated Bcl-2 protein (the anti-apoptotic factor) and upregulated Bax protein (pro-apoptotic factor), eventually leading to a reduction in the ratio of Bcl-2/Bax proteins. Furthermore, oridonin induced the release of cytochrome c from the mitochondria to the cytosol and the activation of caspase-3. Taken together, the current study suggested that oridonin induced apoptosis in SGC-7901 cells via the mitochondrial signal pathway, which may represent one of the major mechanisms of oridonin-mediated apoptosis in SGC-7901 cells.

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“…It is known that repeated instillations (three times over 12 h) of 1.0% atropine sulfate is enough to induce dry eye in the rabbit [44], because of an inhibitory effect on stimulated tear secretion from the main lacrimal gland [16]. Moreover, cytotoxic effects in vitro of 0.03% atropine on human corneal epithelial cells have been reported [45]. Accordingly, our data also indicate that primary human corneal epithelial cells (HCE-F) grown four days in the continuous presence of atropine show signs of toxicity and decreased survival.…”

Section: Discussionmentioning

confidence: 99%

Atropine Differentially Modulates ECM Production by Ocular Fibroblasts, and Its Ocular Surface Toxicity Is Blunted by Colostrum

et al. 2020

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Background: The etiology and the mechanism behind atropine treatment of progressive myopia are still poorly understood. Our study addressed the role of scleral and choroidal fibroblasts in myopia development and atropine function. Methods: Fibroblasts treated in vitro with atropine or 7-methylxanthine were tested for ECM production by Western blotting. Corneal epithelial cells were treated with atropine in the presence or absence of colostrum or fucosyl-lactose, and cell survival was evaluated by the MTT metabolic test. Results: Atropine and 7-methyl-xanthine stimulated collagen I and fibronectin production in scleral fibroblasts, while they inhibited their production in choroidal fibroblasts. Four days of treatment with atropine of corneal epithelial cells significantly decreased cell viability, which could be prevented by the presence of colostrum or fucosyl-lactose. Conclusions: Our results show that atropine may function in different ways in different eye districts, strengthening the scleral ECM and increasing permeability in the choroid. The finding that colostrum or fucosyl-lactose attenuate the corneal epithelial toxicity after long-term atropine treatment suggests the possibility that both compounds can efficiently blunt its toxicity in children subjected to chronic atropine treatment.

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Cytotoxicity of atropine to human corneal epithelial cells by inducing cell cycle arrest and mitochondrion-dependent apoptosis

Cited by 26 publications

References 43 publications

Differentiated mitochondrial function in mouse 3T3 fibroblasts and human epithelial or endothelial cells in response to chemical exposure

Differentiated mitochondrial function in mouse 3T3 fibroblasts and human epithelial or endothelial cells in response to chemical exposure

Oridonin induces apoptosis through the mitochondrial pathway in human gastric cancer SGC-7901 cells

Atropine Differentially Modulates ECM Production by Ocular Fibroblasts, and Its Ocular Surface Toxicity Is Blunted by Colostrum

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