Combretastatin A-4 and structurally related triazole analogues induce caspase-3 and reactive oxygen species-dependent cell death in PC12 cells

The neuroprotective mechanisms of Crataegus pinnatifida extracts and crataegolic acid were studied using paraquat induced cytotoxicity in PC12 cells. C. pinnatifida extracts were prepared using hexane, ethyl acetate, and 95% ethanol. Additionally, crataegolic acid (also known as maslinic acid) was found in C. pinnatifida extracts. Assessment methods included the examinations of cytotoxicity, intracellular reactive oxygen species and calcium changes, activity of caspase-3 and α-synuclein, apoptotic cell death, and the expression levels of the B-cell lymphoma 2 (Bcl-2) and BCL2-associated X (Bax) proteins to investigate the neuroprotective mechanisms of C. pinnatifida extracts and its active component, crataegolic acid. The three extracts and crataegolic acid exhibited potent neuroprotective actions against paraquat induced PC12 cell apoptosis at 5–20µg/mL and 80–100µM concentrations, respectively. The key protective mechanisms included decreasing cell apoptosis, upregulating Bcl-2 protein levels, and downregulating Bax protein levels. The 95% ethanol extract also decreased paraquat induced reactive oxygen species production, calcium overloading, and caspase-3 and α-synuclein activities. The beneficial effects of these extracts could be explained by the active component, crataegolic acid that also inhibited paraquat-induced apoptosis through the suppression of reactive oxygen species generation and the caspase-3 signaling pathway.

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Reactive oxygen species and caspase activation mediate silica-induced apoptosis in alveolar macrophages

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.2001.280.1.l10 ◽

2001 ◽

Vol 280 (1) ◽

pp. L10-L17 ◽

Cited By ~ 32

Author(s):

Han-Ming Shen ◽

Zhuo Zhang ◽

Qi-Feng Zhang ◽

Choon-Nam Ong

Keyword(s):

Reactive Oxygen Species ◽

Cell Death ◽

Alveolar Macrophages ◽

Caspase 3 ◽

Reactive Oxygen ◽

Parp Cleavage ◽

Oxygen Species ◽

Caspase Activation ◽

Caspase 9 ◽

Induced Apoptosis

Alveolar macrophages (AMs) are the principal target cells of silica and occupy a key position in the pathogenesis of silica-related diseases. Silica has been found to induce apoptosis in AMs, whereas its underlying mechanisms involving the initiation and execution of apoptosis are largely unknown. The main objective of the present study was to examine the form of cell death caused by silica and the mechanisms involved. Silica-induced apoptosis in AMs was evaluated by terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling assay and cell cycle/DNA content analysis. The elevated level of reactive oxygen species (ROS), caspase-9 and caspase-3 activation, and poly(ADP-ribose) polymerase (PARP) cleavage in silica-treated AMs were also determined. The results showed that there was a temporal pattern of apoptotic events in silica-treated AMs, starting with ROS formation and followed by caspase-9 and caspase-3 activation, PARP cleavage, and DNA fragmentation. Silica-induced apoptosis was significantly attenuated by a caspase-3 inhibitor, N-acetyl-Asp-Glu-Val-Asp aldehyde, and ebselen, a potent antioxidant. These findings suggest that apoptosis is an important form of cell death caused by silica exposure in which the elevated ROS level that results from silica exposure may act as an initiator, leading to caspase activation and PARP cleavage to execute the apoptotic process.

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Mefloquine, an anti‐malaria agent, causes reactive oxygen species‐dependent cell death in mast cells via a secretory granule‐mediated pathway

Pharmacology Research & Perspectives ◽

10.1002/prp2.66 ◽

2014 ◽

Vol 2 (6) ◽

Cited By ~ 16

Author(s):

Aida Paivandy ◽

Gabriela Calounova ◽

Behdad Zarnegar ◽

Helena Öhrvik ◽

Fabio R. Melo ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Cell Death ◽

Mast Cells ◽

Secretory Granule ◽

Reactive Oxygen ◽

Oxygen Species ◽

Dependent Cell

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Fructose‐1,6‐bisphosphate induces generation of reactive oxygen species and activation of p53‐dependent cell death in human endometrial cancer cells

Journal of Applied Toxicology ◽

10.1002/jat.4091 ◽

2020 ◽

Author(s):

Bruna Pasqualotto Costa ◽

Marcella Tornquist Nassr ◽

Fernando Mendonça Diz ◽

Leonardo Pfeiff Carlessi ◽

Krist Helen Antunes Fernandes ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Cell Death ◽

Endometrial Cancer ◽

Cancer Cells ◽

Reactive Oxygen ◽

Oxygen Species ◽

Dependent Cell ◽

Fructose 1,6 Bisphosphate

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Fisetin Protects PC12 Cells from Tunicamycin-Mediated Cell Death via Reactive Oxygen Species Scavenging and Modulation of Nrf2-Driven Gene Expression, SIRT1 and MAPK Signaling in PC12 Cells

International Journal of Molecular Sciences ◽

10.3390/ijms18040852 ◽

2017 ◽

Vol 18 (4) ◽

pp. 852 ◽

Cited By ~ 23

Author(s):

Jui-Hung Yen ◽

Pei-Shan Wu ◽

Shu-Fen Chen ◽

Ming-Jiuan Wu

Keyword(s):

Gene Expression ◽

Reactive Oxygen Species ◽

Cell Death ◽

Pc12 Cells ◽

Reactive Oxygen ◽

Mapk Signaling ◽

Oxygen Species

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Reactive oxygen species-provoked mitochondria-dependent cell death during ageing of elm (Ulmus pumilaL.) seeds

The Plant Journal ◽

10.1111/tpj.12737 ◽

2015 ◽

Vol 81 (3) ◽

pp. 438-452 ◽

Cited By ~ 40

Author(s):

Yu Wang ◽

Ying Li ◽

Hua Xue ◽

Hugh W. Pritchard ◽

Xiaofeng Wang

Keyword(s):

Reactive Oxygen Species ◽

Cell Death ◽

Reactive Oxygen ◽

Oxygen Species ◽

Dependent Cell

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Bufalin Induces Reactive Oxygen Species Dependent Bax Translocation and Apoptosis in ASTC-a-1 Cells

Evidence-based Complementary and Alternative Medicine ◽

10.1093/ecam/nep082 ◽

2011 ◽

Vol 2011 ◽

pp. 1-12 ◽

Cited By ~ 21

Author(s):

Lei Sun ◽

Tongsheng Chen ◽

Xiaoping Wang ◽

Yun Chen ◽

Xunbin Wei

Keyword(s):

Reactive Oxygen Species ◽

Cell Death ◽

Molecular Mechanisms ◽

Caspase 3 ◽

Temporal Dynamics ◽

Reactive Oxygen ◽

Ros Generation ◽

Ros Production ◽

Oxygen Species ◽

Induced Apoptosis

Bufalin has been shown to induce cancer cell death through apoptotic pathways. However, the molecular mechanisms are not well understood. In this study, we used the confocal fluorescence microscopy (CFM) to monitor the spatio-temporal dynamics of reactive oxygen species (ROS) production, Bax translocation and caspase-3 activation during bufalin-induced apoptosis in living human lung adenocarcinoma (ASTC-a-1) cells. Bufalin induced ROS production and apoptotic cell death, demonstrated by Hoechst 33258 staining as well as flow cytometry analysis. Bax redistributed from cytosol to mitochondria from 12 to 48 h after bufalin treatment in living cells expressed with green fluorescent protein Bax. Treatment with the antioxidantN-acetyl-cysteine (NAC), a ROS scavenger, inhibited ROS generation and Bax translocation and led to a significant protection against bufalin-induced apoptosis. Our results also revealed that bufalin induced a prominent increase of caspase-3 activation blocked potently by NAC. Taken together, bufalin induced ROS-mediated Bax translocation, mitochondrial permeability transition and caspase-3 activation, implying that bufalin induced apoptosis via ROS-dependent mitochondrial death pathway in ASTC-a-1 cells.

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