scholarly journals Morphine inhibits doxorubicin-induced reactive oxygen species generation and nuclear factor κB transcriptional activation in neuroblastoma SH-SY5Y cells

2007 ◽  
Vol 406 (2) ◽  
pp. 215-221 ◽  
Author(s):  
Xin Lin ◽  
Qing Li ◽  
Yu-Jun Wang ◽  
Ya-Wen Ju ◽  
Zhi-Qiang Chi ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Transcriptional Activation ◽  
Caspase 3 ◽  
Reactive Oxygen Species Generation ◽  
Nuclear Factor Κb ◽  
Ros Generation ◽  
Nuclear Factor ◽  
Oxygen Species ◽  
Cytochrome C Release ◽  
Apoptotic Activity

Morphine is recommended as a first-line opioid analgesic in the pain management of cancer patients. Accumulating evidence shows that morphine has anti-apoptotic activity, but its impact on the therapeutic applications of antineoplastic drugs is not well known. The present study was undertaken to test the hypothesis that morphine might antagonize the pro-apoptotic activity of DOX (doxorubicin), a commonly used antitumour drug for the treatment of neuroblastoma, in cultured SH-SY5Y cells. In the present study we demonstrated that morphine suppressed DOX-induced inhibition of cell proliferation and programmed cell death in a concentration-dependent, and naloxone as well as pertussis toxin-irreversible, manner. Further studies showed that morphine inhibited ROS (reactive oxygen species) generation, and prevented DOX-mediated caspase-3 activation, cytochrome c release and changes of Bax and Bcl-2 protein expression. The antioxidant NAC (N-acetylcysteine) also showed the same effects as morphine on DOX-induced ROS generation, caspase-3 activation and cytochrome c release and changes in Bax (Bcl-2-associated X protein) and Bcl-2 protein expression. Additionally, morphine was found to suppress DOX-induced NF-κB (nuclear factor κB) transcriptional activation via a reduction of IκBα (inhibitor of nuclear factor κB) degradation. These present findings support the hypothesis that morphine can inhibit DOX-induced neuroblastoma cell apoptosis by the inhibition of ROS generation and mitochondrial cytochrome c release, as well as by blockade of NF-κB transcriptional activation, and suggests that morphine might have an impact on the antitumour efficiency of DOX.

scholarly journals Hypericin Enhances Paclitaxel-Induced B16-F10 Cell Apoptosis by Activating a Cytochrome c Release–Dependent Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Liyun Sun ◽  
Zixuan Li ◽  
Huoli Shang ◽  
Xiujuan Xin
Keyword(s):  
Cytochrome C ◽  
Caspase 3 ◽  
Chromatin Condensation ◽  
Combined Treatment ◽  
Inhibitory Effect ◽  
Combination Group ◽  
Oxygen Species ◽  
Apoptotic Body ◽  
Cytochrome C Release ◽  
Dependent Pathway

The enhanced inhibitory effect of paclitaxel (PTX) combined with hypericin (HY) on B16-F10 cells may be realized through the ROS-related cytochrome c release pathway. The apoptotic characteristics of the B16-F10 cells, such as DNA fragmentation, chromatin condensation, and apoptotic body formation, were all enhanced in the combined treatment group. Further investigation showed that the combination of paclitaxel and HY could increase the level of mitochondrial damage and the concentration of cytochrome c, causing the expression of caspase-3 and the cleavage of PARP.1. Compared with paclitaxel or HY alone, the level of reactive oxygen species (ROS) increased significantly, while glutathione reductase (GR) activity and intracellular glutathione (GSH) levels decreased significantly in the combination group.

scholarly journals The influence of melatonin on apoptosis of human neutrophils

2019 ◽  
Vol 73 ◽  
pp. 81-91
Author(s):  
Sylwia Mańka ◽  
Zbigniew Baj ◽  
Ewa Majewska
Keyword(s):  
Cytochrome C ◽  
Caspase 3 ◽  
Control Level ◽  
Human Neutrophils ◽  
Ros Generation ◽  
Main Role ◽  
Spontaneous Apoptosis ◽  
Cytochrome C Release ◽  
Tnf Α ◽  
Induced Apoptosis

Aim: Melatonin (Mel) besides its main role in circadian and seasonal rhythm coordination, plays a role in immunoregulation and inflammatory responses. The melatonin’s ability to modulate apoptosis is one of its important roles related to its effect on immune system but the exact effect of its action and the mechanisms of apoptosis control by melatonin remain still unclear. The goal of our study was to examine the involvement of melatonin in the apoptosis of human neutrophils in vitro and possible mechanisms of this action. Material/Methods: We measured the effect of melatonin on the spontaneous and TNF-α-induced apoptosis of human neutrophils using propidium iodide and Annexin-V and on caspase-3 activation, apoptosis-related surface antigen expressions, intracellular reactive oxygen species (ROS) generation and cytochrome c release using flow cytometry and commercial reagents. Results: Melatonin does not affect spontaneous apoptosis of human neutrophils and mitochondrial cytochrome c release but protects the cells from the significant rise of TNF-α-induced apoptosis and cytochrome c release. Intracellular ROS generation in PMA-stimulated neutrophils did not change after the influence of melatonin but the significant drop of ROS generation in neutrophils stimulated with TNF- α was upregulated to the control level after preincubation of the neutrophils with melatonin. Melatonin did not change significantly Fas, Fas-L and active caspase-3 expressions in neutrophils. Conclusions: Melatonin does not affect the spontaneous apoptosis, however, inhibits TNF-α-induced apoptosis of human neutrophils. Our findings suggest that the intrinsic pathway of the process is a result of the melatonin induced mitochondrial alterations.

scholarly journals Reactive oxygen species stimulate VEGF production from C2C12skeletal myotubes through a PI3K/Akt pathway

2001 ◽  
Vol 280 (4) ◽  
pp. L585-L592 ◽  
Author(s):  
Ioanna Kosmidou ◽  
Angeliki Xagorari ◽  
Charis Roussos ◽  
Andreas Papapetropoulos
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Nuclear Factor Κb ◽  
Ros Generation ◽  
Nuclear Factor ◽  
Oxygen Species ◽  
Akt Phosphorylation ◽  
Skeletal Myotubes ◽  
Endothelial Growth Factor ◽  
Vegf Release

Vascular endothelial growth factor (VEGF) is a potent angiogenic stimulus, the expression of which increases in skeletal muscle after exercise. Because exercise is also accompanied by increased intramuscular reactive oxygen species (ROS) generation, we tested the hypothesis that ROS stimulate VEGF production from skeletal myotubes. Differentiated C2C12skeletal myotubes exposed to ROS-producing agents exhibited a concentration-dependent increase in VEGF production, whereas undifferentiated myoblasts did not respond to oxidants. Moreover, conditioned medium from ROS-treated myotubes increased the bovine lung microvascular cell proliferation rate. To study the mechanism(s) involved in the stimulation of VEGF production by ROS, myotubes were pretreated with a selective phosphatidylinositol 3-kinase (PI3K) inhibitor, LY-294002, before being exposed to hydrogen peroxide or pyrogallol. LY-294002 attenuated both Akt phosphorylation and VEGF production. In addition, oxidants increased nuclear factor-κB-dependent promoter activity in transiently transfected myotubes; however, pretreatment with the pharmacological inhibitor of nuclear factor-κB, diethyldithiocarbamate, did not affect the oxidant-stimulated VEGF release. We conclude that ROS induce VEGF release from myotubes via a PI3K/Akt-dependent pathway.

Sign in / Sign up

Export Citation Format

Share Document