The radical scavenger edaravone enhances the anti-tumor effects of CPT-11 in murine colon cancer by increasing apoptosis via inhibition of NF-κB

Kokura, Satoshi; Yoshida, Norimasa; Sakamoto, Naoyuki; Ishikawa, Takeshi; Takagi, Tomohisa; Higashihara, Hiroshi; Nakabe, Nami; Handa, Osamu; Naito, Yuji; Yoshikawa, Toshikazu

doi:10.1016/j.canlet.2005.06.039

Cited by 45 publications

(25 citation statements)

References 28 publications

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“…In addition, Eda not only had antioxidant roles, but also protected cells from apoptosis [16,17] . However, little information is available on antioxidant Eda in regulating the Bcl-2/Bax apoptotic pathway via mitochondria after CoCl 2 injury at cellular level.…”

Section: Discussionmentioning

confidence: 95%

Protective effects of edaravone against cobalt chloride-induced apoptosis in PC12 cells

2009

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Objective To investigate the neuroprotective effects of edaravone (Eda) on cobalt chloride (CoCl 2 )-induced oxidative stress and apoptosis in cultured PC12 cells as well as the underlying mechanisms. Methods PC12 cells impaired by CoCl 2 were used as the cell model of hypoxia. MTT (methyl thiazolyl tetrazolium) was used to assay the viability of the PC12 cells exposed to Eda with gradient concentrations; Hochest 33258 stain assay was used to analyze the apoptosis ratio of the PC12 cells; Bcl-2 and Bax protein levels in PC12 cells were examined by western blotting. ROS level, the mitochondrial transmembrane potential and caspase-3 activity in each group were detected by spectrofluorometer. Results CoCl 2 treatment caused the loss of cell viability in PC12 cells, which was associated with the elevation of apoptotic rate, the formation of ROS and the disruption of mitochondrial transmembrane potential. CoCl 2 also significantly induced the upregulation of Bax/Bcl-2 ratio and the activation of caspase-3. In contrast, Eda significantly reversed these phenotypes, with its maximum protective effect at 0.1 μmol/L. Conclusion These results indicated that Eda could protect PC12 cells from CoCl 2 -induced cytotoxicity, and this protection might be ascribed to its anti-oxidative and anti-apoptotic activities.

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Section: Discussionmentioning

confidence: 95%

Protective effects of edaravone against cobalt chloride-induced apoptosis in PC12 cells

2009

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“…A concept of a nuclear-to-cytoplasmic signaling pathway was postulated to explain, such a signaling mechanism by Stein et al in 1989 [39]. However, dissection of NF-κB activation pathways induced by genotoxic agents is complicated by the co-induction of different types of DNA damages as well as other cell stresses, including oxidative stress in different cellular compartments (e.g., [40][41][42][43][44][45], Figure 1). Thus, unlike NF-κB signaling induced by cell surface receptors where the signal initiation event can be precisely defined, the necessary and sufficient signal initiation event induced by various genotoxic agents is still being addressed in the literature.…”

Section: A Signal Transduction Paradoxmentioning

confidence: 99%

Nuclear initiated NF-κB signaling: NEMO and ATM take center stage

2010

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A large body of literature describes elaborate NF-κB signaling networks induced by inflammatory and immune signals. Decades of research has revealed that transcriptionally functional NF-κB dimers are activated by two major pathways, canonical and non-canonical. Both pathways involve the release of NF-κB dimers from inactive cytoplasmic complexes to cause their nuclear translocation to modulate gene expression programs and biological responses. NF-κB is also responsive to genotoxic agents; however, signal communication networks that are initiated in the nucleus following DNA damage induction are less defined. Evidence in the literature supports the presence of such signaling pathways induced by multiple distinct genotoxic agents, resulting in the activation of cytoplasmic IKK complex. An example is a pathway that involves the DNA damage-responsive kinase ataxia telangiectasia mutated (ATM) and a series of post-translational modifications of NF-κB essential modulator (NEMO) in the nucleus of a genotoxinexposed cell. Recent evidence also suggests that this nuclear-initiated NF-κB signaling pathway plays significant physiological and pathological roles, particularly in lymphocyte development and human cancer progression. This review will summarize these new developments, while identifying significant unanswered questions and providing new hypotheses that may be addressed in future studies.

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“…Using a rat model of transient middle cerebral artery occlusion (MCAO), the data showed that daily treatment with edaravone reduced cortical infarction volume. In addition, edaravone not only has antioxident action, but also protects cells from apoptosis (Kokura et al, 2005;Suzuki et al, 2005). However, little information is available on antioxidant edaravone in regulating the Bcl-2/Bax apoptotic pathway via mitochondria after OGD-reperfusion injury at cellular level.…”

Section: Introductionmentioning

confidence: 99%

Edaravone protects PC12 cells from ischemic-like injury via attenuating the damage to mitochondria

Song¹,

Li²,

Li³

et al. 2006

J. Zhejiang Univ. - Sci. B

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Background: Edaravone had been validated to effectively protect against ischemic injuries. In this study, we investigated the protective effect of edaravone by observing the effects on anti-apoptosis, regulation of Bcl-2/Bax protein expression and recovering from damage to mitochondria after OGD (oxygen-glucose deprivation)-reperfusion. Methods: Viability of PC12 cells which were injured at different time of OGD injury, was quantified by measuring MTT (2-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) staining. In addition, PC12 cells' viability was also quantified after their preincubation in different concentration of edaravone for 30 min followed by (OGD). Furthermore, apoptotic population of PC12 cells that reinsulted from OGD-reperfusion with or without preincubation with edaravone was determined by flow cytometer analysis, electron microscope and Hoechst/PI staining. Finally, change of Bcl-2/Bax protein expression was detected by Western blot. Results: (1) The viability of PC12 cells decreased with time (1~12 h) after OGD. We regarded the model of OGD 2 h, then replacing DMEM (Dulbecco's Modified Eagle's Medium) for another 24 h as an OGD-reperfusion in this research. Furthermore, most PC12 cells were in the state of apoptosis after OGD-reperfusion. (2) The viability of PC12 cells preincubated with edaravone at high concentrations (1, 0.1, 0.01 µmol/L) increased significantly with edaravone protecting PC12 cells from apoptosis after OGD-reperfusion injury. (3) Furthermore, edaravone attenuates the damage of OGD-reperfusion on mitochondria and regulated Bcl-2/Bax protein imbalance expression after OGD-reperfusion. Conclusion: Neuroprotective effects of edaravone on ischemic or other brain injuries may be partly mediated through inhibition of Bcl-2/Bax apoptotic pathways by recovering from the damage of mitochondria.

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The radical scavenger edaravone enhances the anti-tumor effects of CPT-11 in murine colon cancer by increasing apoptosis via inhibition of NF-κB

Cited by 45 publications

References 28 publications

Protective effects of edaravone against cobalt chloride-induced apoptosis in PC12 cells

Protective effects of edaravone against cobalt chloride-induced apoptosis in PC12 cells

Nuclear initiated NF-κB signaling: NEMO and ATM take center stage

Edaravone protects PC12 cells from ischemic-like injury via attenuating the damage to mitochondria

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