scholarly journals Celastrol-induced apoptosis in human nasopharyngeal carcinoma is associated with the activation of the death receptor and the mitochondrial pathway

2017 ◽  
Vol 14 (2) ◽  
pp. 1683-1690 ◽  
Author(s):  
Heng-Fu Lin ◽  
Ming-Ju Hsieh ◽  
Yi-Ting Hsi ◽  
Yu-Sheng Lo ◽  
Yi-Ching Chuang ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Death Receptor ◽  
Mitochondrial Pathway ◽  
Human Nasopharyngeal Carcinoma ◽  
Induced Apoptosis

scholarly journals Colistin-Induced Nephrotoxicity in Mice Involves the Mitochondrial, Death Receptor, and Endoplasmic Reticulum Pathways

2014 ◽  
Vol 58 (7) ◽  
pp. 4075-4085 ◽  
Author(s):  
Chongshan Dai ◽  
Jichang Li ◽  
Shusheng Tang ◽  
Jian Li ◽  
Xilong Xiao
Keyword(s):  
Endoplasmic Reticulum ◽  
Death Receptor ◽  
Mitochondrial Pathway ◽  
Protective Role ◽  
Limiting Factor ◽  
Death Domain ◽  
Tubular Necrosis ◽  
Apoptosis Pathways ◽  
Group A ◽  
Induced Apoptosis

ABSTRACTNephrotoxicity is the dose-limiting factor for colistin, but the exact mechanism is unknown. This study aimed to investigate the roles of the mitochondrial, death receptor, and endoplasmic reticulum pathways in colistin-induced nephrotoxicity. Mice were intravenously administered 7.5 or 15 mg of colistin/kg of body weight/day (via a 3-min infusion and divided into two doses) for 7 days. Renal function, oxidative stress, and apoptosis were measured. Representative biomarkers involved in the mitochondrial, death receptor, and endoplasmic reticulum pathways were investigated, and the key markers involved in apoptosis and autophagy were examined. After 7-day colistin treatment, significant increase was observed with blood urea nitrogen, serum creatinine, and malondialdehyde, while activities of superoxide dismutase (SOD) and catalase decreased in the kidneys. Acute tubular necrosis and mitochondrial dysfunction were detected, and colistin-induced apoptosis was characterized by DNA fragmentation, cleavage of poly(ADP-ribose) polymerase (PARP-1), increase of 8-hydroxydeoxyguanosine (8-OHdG), and activation of caspases (caspase-8, -9, and -3). It was evident that colistin-induced apoptosis involved the mitochondrial pathway (downregulation of Bcl-2 and upregulation of cytochrome C [cytC] and Bax), death receptor pathway (upregulation of Fas, FasL, and Fas-associated death domain [FADD]), and endoplasmic reticulum pathway (upregulation of Grp78/Bip, ATF6, GADD153/CHOP, and caspase-12). In the 15-mg/kg/day colistin group, expression of the cyclin-dependent kinase 2 (CDK2) and phosphorylated JNK (p-JNK) significantly increased (P< 0.05), while in the 7.5-mg/kg/day colistin group, a large number of autophagolysosomes and classic autophagy were observed. Western blot results of Beclin-1 and LC3B indicated that autophagy may play a protective role in colistin-induced nephrotoxicity. In conclusion, this is the first study to demonstrate that all three major apoptosis pathways and autophagy are involved in colistin-induced nephrotoxicity.

scholarly journals CLEAR AS MUD: THE TYPE I/TYPE II MODEL FOR DEATH RECEPTOR-INDUCED APOPTOSIS

2006 ◽  
Vol 43 (2) ◽  
Author(s):  
David Michael Conrad
Keyword(s):  
Death Receptor ◽  
Mitochondrial Pathway ◽  
Type I ◽  
Biological Processes ◽  
Type Ii ◽  
Type Ii Cell ◽  
Mort Cellulaire ◽  
Induced Apoptosis ◽  
First Time ◽  
The Relationship

Apoptosis is a highly organized form of cell death that plays an important regulatory role in many biological processes. The relationship between the two classical signalling pathways of apoptosis, the “death receptor” and “mitochondrial” pathways, was only vaguely appreciated until 1998, when death receptor pathway-mediated activation of the mitochondrial pathway was clearly demonstrated for the first time. The “type I/type II” model of death receptor-mediated apoptosis was proposed and subsequently adopted for use in categorizing cells according to the involvement of the mitochondrion duringdeath receptor-induced apoptosis. Since that time, however, different interpretations of the type I/type II cell definition have appeared in the literature and, consequently, the meaning of type I and type II cells has become less clear.L’apoptose est une forme de mort cellulaire très structurée qui joue un rôle important de régulation dans un grand nombre de processus biologiques. La relation entre les deux voies de signalisation traditionnelles de l’apoptose, la voie des « récepteurs de mort » et la voie mitochondriale, n’était connue que vaguement avant 1998, l'année où l’activation de la voie mitochondriale par l’intermédiaire de la voie des récepteurs de mort a été clairement démontrée pour la première fois. Le modèle « type I / type II » d’apoptose par l’intermédiaire des récepteurs de mort a été proposé puis adopté auxfins de catégorisation des cellules en fonction de la participation des mitochondries à cette apoptose. Depuis, différentes interprétations ont toutefois été formulées dans des ouvrages scientifiques quant à la définition des cellules de type I et de type II et, par conséquent, la signification de « cellules de type I » et de « cellules de type II » est devenue moins évidente.

Indole-3-Carbinol Inhibits Nasopharyngeal Carcinoma

2010 ◽  
Vol 29 (2) ◽  
pp. 185-192 ◽  
Author(s):  
Wei Zhu ◽  
Wenxue Li ◽  
Guangyu Yang ◽  
Quanxin Zhang ◽  
Ming Li ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Nasopharyngeal Carcinoma ◽  
Glutathione Peroxidase ◽  
Tumor Growth ◽  
Caspase 3 ◽  
Caspase 9 ◽  
Human Nasopharyngeal Carcinoma ◽  
Induced Apoptosis

This study explored the effects of indole-3-carbinol on the proliferation of human nasopharyngeal carcinoma, both in vitro and in vivo, and the underlying mechanisms in inducing apoptosis of CNE1 cells. Proliferation, apoptosis, malondialdehyde, superoxide dismutase, glutathione peroxidase, expressions of caspase-9, and caspase-3 in human nasopharyngeal carcinoma cells CNE1 were examined. Indole-3-carbinol suppressed proliferation, induced apoptosis, decreased malondialdehyde level, increased the activity of superoxide dismutase and glutathione peroxidase, and up-regulated the expression of active fragments of caspase-9 and caspase-3 both in vitro and in vivo. It was concluded that indole-3-carbinol could inhibit proliferation and induce apoptosis of CNE1 cells and inhibit tumor growth in mice. Increased activity of superoxide dismutase and glutathione peroxidase and activated expression of caspase-9 and caspase-3 were also observed in indole-3-carbinol–treated tumors or tumor cells, suggesting that stress- and apoptosis-related molecules are involved in the indole-3-carbinol–induced apoptosis and inhibition of tumor growth.

scholarly journals Differential Regulation and ATP Requirement for Caspase-8 and Caspase-3 Activation during CD95- and Anticancer Drug–induced Apoptosis

1998 ◽  
Vol 188 (5) ◽  
pp. 979-984 ◽  
Author(s):  
Davide Ferrari ◽  
Ania Stepczynska ◽  
Marek Los ◽  
Sebastian Wesselborg ◽  
Klaus Schulze-Osthoff
Keyword(s):  
Death Receptor ◽  
Mitochondrial Pathway ◽  
Atp Depletion ◽  
Caspase 8 ◽  
Chemotherapeutic Drugs ◽  
Caspase Activation ◽  
Drug Induced ◽  
Regulatory Pathways ◽  
Atp Production ◽  
Induced Apoptosis

Apoptosis is induced by different stimuli, among them triggering of the death receptor CD95, staurosporine, and chemotherapeutic drugs. In all cases, apoptosis is mediated by caspases, although it is unclear how these diverse apoptotic stimuli cause protease activation. Two regulatory pathways have been recently identified, but it remains unknown whether they are functionally independent or linked to each other. One is mediated by recruitment of the proximal regulator caspase-8 to the death receptor complex. The other pathway is controlled by the release of cytochrome c from mitochondria and the subsequent ATP-dependent activation of the death regulator apoptotic protease-activating factor 1 (Apaf-1). Here, we report that both pathways can be dissected by depletion of intracellular ATP. Prevention of ATP production completely inhibited caspase activation and apoptosis in response to chemotherapeutic drugs and staurosporine. Interestingly, caspase-8, whose function appeared to be restricted to death receptors, was also activated by these drugs under normal conditions, but not after ATP depletion. In contrast, inhibition of ATP production did not affect caspase activation after triggering of CD95. These results suggest that chemotherapeutic drug–induced caspase activation is entirely controlled by a receptor-independent mitochondrial pathway, whereas CD95-induced apoptosis can be regulated by a separate pathway not requiring Apaf-1 function.

Norcantharidin induce apoptosis in human nasopharyngeal carcinoma through caspase and mitochondrial pathway

2017 ◽  
Vol 33 (3) ◽  
pp. 343-350 ◽  
Author(s):  
Andy Wei-Ge Chen ◽  
Yen-Shuo Tseng ◽  
Chia-Chieh Lin ◽  
Yi-Ting Hsi ◽  
Yu-Sheng Lo ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Mitochondrial Pathway ◽  
Human Nasopharyngeal Carcinoma

Capsaicin mediates apoptosis in human nasopharyngeal carcinoma NPC-TW 039 cells through mitochondrial depolarization and endoplasmic reticulum stress

2011 ◽  
Vol 31 (6) ◽  
pp. 539-549 ◽  
Author(s):  
S-W Ip ◽  
S-H Lan ◽  
H-F Lu ◽  
A-C Huang ◽  
J-S Yang ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Nasopharyngeal Carcinoma ◽  
Er Stress ◽  
Molecular Mechanisms ◽  
Human Cancer ◽  
Dependent Manner ◽  
Mitochondrial Depolarization ◽  
Human Nasopharyngeal Carcinoma ◽  
Induced Apoptosis

Capsaicin, a pungent compound found in hot chili peppers, has been reported to have antitumor activities in many human cancer cell lines, but the induction of precise apoptosis signaling pathway in human nasopharyngeal carcinoma (NPC) cells is unclear. Here, we investigated the molecular mechanisms of capsaicin-induced apoptosis in human NPC, NPC-TW 039, cells. Effects of capsaicin involved endoplasmic reticulum (ER) stress, caspase-3 activation and mitochondrial depolarization. Capsaicin-induced cytotoxic effects (cell death) through G0/G1 phase arrest and induction of apoptosis of NPC-TW 039 cells in a dose-dependent manner. Capsaicin treatment triggered ER stress by promoting the production of reactive oxygen species (ROS), increasing levels of inositol-requiring 1 enzyme (IRE1), growth arrest and DNA-damage-inducible 153 (GADD153) and glucose-regulated protein 78 (GRP78). Other effects included an increase in cytosolic Ca2+, loss of the mitochondrial transmembrane potential (ΔΨ m), releases of cytochrome c and apoptosis-inducing factor (AIF), and activation of caspase-9 and -3. Furthermore, capsaicin induced increases in the ratio of Bax/Bcl-2 and abundance of apoptosis-related protein levels. These results suggest that ER stress- and mitochondria-mediated cell death is involved in capsaicin-induced apoptosis in NPC-TW 039 cells.

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