scholarly journals Camalexin Induces Apoptosis via the ROS-ER Stress-Mitochondrial Apoptosis Pathway in AML Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Yang Yang ◽  
Gang Wang ◽  
Wenjun Wu ◽  
Shunnan Yao ◽  
Xiaoyan Han ◽  
...  
Keyword(s):  
Er Stress ◽  
Plant Pathogens ◽  
Leukemic Cells ◽  
Dependent Manner ◽  
Mitochondrial Apoptosis ◽  
Antitumor Effects ◽  
Sod Activity ◽  
Apoptosis Pathway ◽  
Mitochondrial Apoptosis Pathway

Camalexin is a phytoalexin that accumulates in various cruciferous plants upon exposure to environmental stress and plant pathogens. It was shown that camalexin has potent antitumor properties, but its underlying mechanisms are still elusive. In the present study, we evaluated the effects of camalexin on human leukemic cells and normal polymorph nuclear cells. CCK-8 assay was used to determine cell viability after camalexin treatment. Apoptosis, intracellular reactive oxygen species (ROS) levels, and loss of mitochondrial membrane potential (MMP) were measured by flow cytometry. The activity of SOD, catalase, and ratio of GSH/GSSG were assayed. ER stress and apoptotic signaling pathway was examined by Western blot. Xenograft mice were used to verify the effect of camalexin in vivo. Our results indicated that camalexin inhibited viability of leukemic but not normal polymorph nuclear cells. Furthermore, camalexin induces apoptosis via the mitochondrial pathway in a caspase-dependent manner. We also observed ER stress is located upstream of apoptosis induced by camalexin. Besides, ROS levels, SOD activity, CAT activity, and GSSG levels were significantly enhanced while the GSH level was decreased after treatment of camalexin. In addition, the generation of ROS is critical for the ER stress and apoptosis induced by camalexin. Finally, administration of camalexin suppresses xenograft tumor graft growth without obvious toxicity. Taken together, this study indicates that camalexin exerts antitumor effects against leukemia cells via the ROS-ER stress-mitochondrial apoptosis pathway.

scholarly journals N-Acetyl-Serotonin Protects HepG2 Cells from Oxidative Stress Injury Induced by Hydrogen Peroxide

2014 ◽  
Vol 2014 ◽  
pp. 1-15 ◽  
Author(s):  
Jiying Jiang ◽  
Shuna Yu ◽  
Zhengchen Jiang ◽  
Cuihong Liang ◽  
Wenbo Yu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Oxidative Damage ◽  
Hepg2 Cells ◽  
Morphological Changes ◽  
Mitochondrial Apoptosis ◽  
Sod Activity ◽  
Stress Injury ◽  
Apoptosis Pathway ◽  
Mitochondrial Apoptosis Pathway

Oxidative stress plays an important role in the pathogenesis of liver diseases. N-Acetyl-serotonin (NAS) has been reported to protect against oxidative damage, though the mechanisms by which NAS protects hepatocytes from oxidative stress remain unknown. To determine whether pretreatment with NAS could reduce hydrogen peroxide- (H2O2-) induced oxidative stress in HepG2 cells by inhibiting the mitochondrial apoptosis pathway, we investigated the H2O2-induced oxidative damage to HepG2 cells with or without NAS using MTT, Hoechst 33342, rhodamine 123, Terminal dUTP Nick End Labeling Assay (TUNEL), dihydrodichlorofluorescein (H2DCF), Annexin V and propidium iodide (PI) double staining, immunocytochemistry, and western blot. H2O2produced dramatic injuries in HepG2 cells, represented by classical morphological changes of apoptosis, increased levels of malondialdehyde (MDA) and intracellular reactive oxygen species (ROS), decreased activity of superoxide dismutase (SOD), and increased activities of caspase-9 and caspase-3, release of cytochrome c (Cyt-C) and apoptosis-inducing factor (AIF) from mitochondria, and loss of membrane potential (ΔΨm). NAS significantly inhibited H2O2-induced changes, indicating that it protected against H2O2-induced oxidative damage by reducing MDA levels and increasing SOD activity and that it protected the HepG2 cells from apoptosis through regulating the mitochondrial apoptosis pathway, involving inhibition of mitochondrial hyperpolarization, release of mitochondrial apoptogenic factors, and caspase activity.

scholarly journals Myricitrin Protects against Doxorubicin-Induced Cardiotoxicity by Counteracting Oxidative Stress and Inhibiting Mitochondrial Apoptosis via ERK/P53 Pathway

2016 ◽  
Vol 2016 ◽  
pp. 1-16 ◽  
Author(s):  
Jing Sun ◽  
Guibo Sun ◽  
Xiaolan Cui ◽  
Xiangbao Meng ◽  
Meng Qin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Damage ◽  
Mitochondrial Apoptosis ◽  
Mechanism Study ◽  
Apoptosis Pathway ◽  
Mitochondrial Apoptosis Pathway ◽  
Myocardial Apoptosis ◽  
Underlying Mechanisms

Doxorubicin (Dox) is one of the most effective and widely used anthracycline antineoplastic antibiotics. Unfortunately, the use of Dox is limited by its cumulative and dose-dependent cardiac toxicity. Myricitrin, a natural flavonoid which is isolated from the ground bark ofMyrica rubra, has recently been found to have a strong antioxidative effect. This study aimed to evaluate the possible protective effect of myricitrin against Dox-induced cardiotoxicity and the underlying mechanisms. An in vivo investigation in SD rats demonstrated that myricitrin significantly reduced the Dox-induced myocardial damage, as indicated by the decreases in the cardiac index, amelioration of heart pathological injuries, and decreases in the serum cardiac enzyme levels. In addition, in vitro studies showed that myricitrin effectively reduced the Dox-induced cell toxicity. Further study showed that myricitrin exerted its function by counteracting oxidative stress and increasing the activities of antioxidant enzymes. Moreover, myricitrin suppressed the myocardial apoptosis induced by Dox, as indicated by decreases in the activation of caspase-3 and the numbers of TUNEL-positive cells, maintenance of the mitochondrial membrane potential, and increase in the Bcl-2/Bax ratio. Further mechanism study revealed that myricitrin-induced suppression of myocardial apoptosis relied on the ERK/p53-mediated mitochondrial apoptosis pathway.

scholarly journals Triptolide Induces Leydig Cell Apoptosis by Disrupting Mitochondrial Dynamics in Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Linyan Lv ◽  
Yajie Chang ◽  
Yanqing Li ◽  
Haicheng Chen ◽  
Jiahui Yao ◽  
...  
Keyword(s):  
Leydig Cell ◽  
Cell Apoptosis ◽  
Mitochondrial Dynamics ◽  
Reproductive Toxicity ◽  
Mitochondrial Apoptosis ◽  
Mitochondrial Dynamic ◽  
Apoptosis Pathway ◽  
Mitochondrial Apoptosis Pathway

Triptolide is widely used in the clinical treatment of various diseases. Side effects, including reproductive toxicity to male patients, limit its application. However, no detailed mechanisms or potential intervention targets have been reported. In this study, we show that triptolide activated the mitochondrial apoptosis pathway in rat testicular Leydig cells and induced apoptosis both in vivo and in vitro, which may cause hypoleydigism and impair spermatogenesis. Mechanistically, triptolide-induced dynamin-related protein 1 (Drp1) overexpression, which interfered with mitochondrial dynamic stability to activate the mitochondrial apoptosis pathway. Mdivi-1, a selective Drp1 inhibitor, partially reversed the mitochondrial dynamic disturbance and rat testicular Leydig cell apoptosis induced by triptolide. Inhibiting Drp1 over-activation may be a new strategy for mitigating the reproductive toxicity of triptolide.

scholarly journals Matrine Exerts Hepatotoxic Effects via the ROS-Dependent Mitochondrial Apoptosis Pathway and Inhibition of Nrf2-Mediated Antioxidant Response

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Longtai You ◽  
Chunjing Yang ◽  
Yuanyuan Du ◽  
Yi Liu ◽  
Gongsen Chen ◽  
...  
Keyword(s):  
Antioxidant Response ◽  
S Phase ◽  
Activity Level ◽  
Heme Oxygenase 1 ◽  
Mitochondrial Apoptosis ◽  
Sod Activity ◽  
Apoptosis Pathway ◽  
Mitochondrial Apoptosis Pathway ◽  
Wide Range ◽  
Hepatotoxic Effect

Matrine, an alkaloid isolated from Sophora flavescens, possesses a wide range of pharmacological properties. However, the use of matrine in clinical practice is limited due to its toxic effects. The present study investigated the roles of mitochondria and reactive oxygen species (ROS) in matrine-induced liver injury. Our results showed that treatment of HL-7702 cells with matrine led to significant and concentration- and time-dependent reductions in their viability, as well as significant and concentration-dependent increases in the number of apoptotic cells and supernatant lactate dehydrogenase (LDH) activity. The treatment led to significant increases in the population of cells in S phase and significant reduction of cell proportion in G0/G1 and G2/M phases. It also significantly and concentration-dependently increased the levels of ROS and malondialdehyde (MDA) but significantly and concentration-dependently reduced superoxide dismutase (SOD) activity, level of reduced glutathione (GSH), and mitochondrial membrane potential (MMP). Matrine treatment significantly and concentration-dependently upregulated the expressions of Bax, p53, p-p53, p21, cyclin E, Fas, cleaved caspase-3, caspase-8, and caspase-9 proteins and downregulated the expressions of Bcl-2, cyclin-dependent kinase 2 (CDK2), and cyclin A. It also significantly promoted the cleavage of poly(ADP-ribose)polymerase (PARP), upregulated Kelch-like ECH-associated protein 1 (Keap1) expression, and downregulated the expressions of cellular total and nuclear Nrf2. Matrine significantly inhibited the expressions of downstream oxidoreductases (Heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductases 1 (NQO-1)) and enhanced the formation of Keap1/Nrf2 protein complex. These results show that the hepatotoxic effect of matrine is exerted via inhibition of Nrf2 pathway, activation of ROS-mediated mitochondrial apoptosis pathway, and cell cycle arrest at S phase. Pretreatment with N-acetyl cysteine (NAC) partially reversed matrine-induced hepatotoxicity.

Homoharringtonine Induced Apoptosis of Leukemic Cell Line MUTZ-1 Cells Is Mediated by the Endoplasmic Reticulum Stress Pathway.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4917-4917 ◽  
Author(s):  
Zhen Cai ◽  
Jie Hu ◽  
Donghua He ◽  
Wenjun Wu ◽  
Liang Gao ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Cell Line ◽  
Binding Protein ◽  
Light And Electron Microscopy ◽  
Leukemic Cells ◽  
Dependent Manner ◽  
Rt Pcr ◽  
Apoptosis Pathway ◽  
Stress Pathway

Abstract The endoplasmic reticulum (ER) is the major organelle for protein synthesis and maturation as well as the regulation of intracellular calcium (Ca2+) homeostasis. The accumulation of unfolded proteins in the ER lumen or depletion of Ca2+ from the ER lumen leads to the ER stress response known as unfold protein response. This response enhances the ability of protein folding by inducing ER resident chaperones such as glucose-regulated stress protein 78 or immunoglobulin heavy-chain binding protein (GRP78/BIP) mRNA and protects the cell from ER stress by splicing of X-box binding protein 1 (XBP-1) mRNA, and synthesis of phosphatidylcholine, the primary phospholipid of the ER membrane. However, when the ER function is severely impaired, the organelle elicits apoptotic signals. One of the components of the ER stress-mediated apoptosis pathway is C/EBP homologous protein (CHOP), also known as growth arrest- and DNA damage-inducible gene 153. Homoharringtonine (HHT), one of the alkaloids from a Chinese natural plant, Cephalotaxus, has currently been used successfully in the treatment of acute and chronic myeloid leukemias and has been shown to induce apoptosis of different types of leukemic cells in vitro. But the mechanism of how HHT causes apoptosis remains unknown. In this study, we investigated the relationship between ER stress and apoptosis of MUTZ-1 cells (cell line of MDS) treated with HHT. HHT induced growth inhibition of MUTZ-1 cells was measured by MTT method. Apoptosis was detected by FACS and observed by light and electron microscopy. Concentration of cystosolic calcium was measured with the spectrofluorometer. The mRNA expression level of CHOP, BIP and XBP1 was detected by semi-quantitative RT-PCR. We found that after exposure of MUTZ-1 to HHT (rang 0.02~0.4ug/ml) for 24 to 72 hours, the IC50 and the percentage of apoptotic MUTZ-1 cells increased in a time and dose dependent manner. Typical apoptotic cells and release of Ca2+ from the cytosolic Ca2+ storage were observed. RT-PCR analysis revealed that mRNAs for ER stress-associated proapoptotic factor CHOP and an ER chaperone BiP, XBP1 are markedly increased at 4 hours after 0.05ug/ml HHT treated and reach the top level at 12hours, then decreased to the level before treatment at 24 hours. Induction of ER stress-responsive proteins (BIP and CHOP) was also observed at 12 hours. These results indicate that HHT could not only inhibit MUTZ-1 growth but also induce MUTZ-1 apoptosis and HHT-induced MUTZ-1 cell death is likely mediated by the ER stress pathway.

scholarly journals Gui-A-Gra Attenuates Testicular Dysfunction in Varicocele-Induced Rats via Oxidative Stress, ER Stress and Mitochondrial Apoptosis Pathway

2020 ◽  
Vol 21 (23) ◽  
pp. 9231
Author(s):  
Keshab Kumar Karna ◽  
Na Young Choi ◽  
Chul Young Kim ◽  
Hye Kyung Kim ◽  
Yu Seob Shin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Er Stress ◽  
B Cell Lymphoma ◽  
Reproductive Hormones ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Control Group ◽  
Mitochondrial Apoptosis ◽  
Apoptosis Pathway ◽  
Mitochondrial Apoptosis Pathway ◽  
Testicular Dysfunction

Gui-A-Gra, a commercial insect powder from Gryllus bimaculatus, is registered as an edible insect by the Korean food and drug administration. The aim of this study was to investigate the effect of Gui-A-Gra on testicular damage induced by experimental left varicocele in male Sprague Dawley rats. A total of 72 rats were randomly divided into the following six groups (12 rats in each group): a normal control group (CTR), a group administrated with Gui-A-Gra 1.63 gm/kg (G1.63), a group administrated with Gui-A-Gra 6.5 gm/kg (G6.5), a varicocele (VC)-induced control group (VC), a VC-induced group administrated with Gui-A-Gra 1.63 gm/kg (VC + G1.63), and a VC-induced group administrated with Gui-A-Gra 6.5 gm/kg (VC + G6.5). Rats were administrated 1.63 or 6.5 gm/kg Gui-A-Gra once daily for 42 days. Indicators of sperm parameters, histopathology, reproductive hormones, oxidative stress, endoplasmic reticulum (ER) stress, inflammation, and mitochondrial apoptosis were analyzed to evaluate effects of Gui-A-Gra on VC-induced testicular dysfunction. Gui-A-Gra administration to VC-induced rats significantly (p < 0.05) increased sperm count and sperm motility, Johnsen score, spermatogenic cell density, serum testosterone, testicular superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase, GPx4, and steroidogenic acute regulatory protein (StAR) level. Moreover, pretreatment with Gui-A-Gra significantly (p < 0.05) decreased terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) positive cells/tubules, serum luteinizing hormone (LH), serum follicle-stimulating hormone (FSH), testicular tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), malondialdehyde (MDA), reactive oxygen species (ROS)/reactive nitrogen species (RNS) level, glucose-regulated protein-78 (Grp-78), phosphorylated c-Jun-N-terminal kinase (p-JNK), phosphorylated inositol-requiring transmembrane kinase/endoribonuclease 1α (p-IRE1α), cleaved caspase-3, and BCL2 associated X protein: B-cell lymphoma 2 (Bax: Bcl2) ratio in VC rats. These results suggest that protective effects of Gui-A-Gra on VC-induced testicular injury might be due to its antioxidant, anti-inflammatory, and androgenic activities that might be mediated via crosstalk of oxidative stress, ER stress, and mitochondrial apoptosis pathway.

Sign in / Sign up

Export Citation Format

Share Document