scholarly journals Ordering of ceramide formation, caspase activation, and mitochondrial changes during CD95- and DNA damage–induced apoptosis

1999 ◽  
Vol 103 (7) ◽  
pp. 971-978 ◽  
Author(s):  
Annemiek D. Tepper ◽  
Evert de Vries ◽  
Wim J. van Blitterswijk ◽  
Jannie Borst
Keyword(s):  
Dna Damage ◽  
Caspase Activation ◽  
Induced Apoptosis

scholarly journals Ordering of ceramide formation, caspase activation, and mitochondrial changes during CD95- and DNA damage–induced apoptosis

1999 ◽  
Vol 103 (9) ◽  
pp. 1363-1363
Author(s):  
Annemiek D. Tepper ◽  
Evert de Vries ◽  
Wim J. van Blitterswijk ◽  
Jannie Borst
Keyword(s):  
Dna Damage ◽  
Caspase Activation ◽  
Induced Apoptosis

Role of p53 in cisplatin-induced tubular cell apoptosis: dependence on p53 transcriptional activity

2004 ◽  
Vol 287 (6) ◽  
pp. F1140-F1147 ◽  
Author(s):  
Man Jiang ◽  
Xiaolan Yi ◽  
Stephen Hsu ◽  
Cong-Yi Wang ◽  
Zheng Dong
Keyword(s):  
Dna Damage ◽  
Cell Death ◽  
Transcriptional Activity ◽  
Tubular Cell ◽  
Caspase Activation ◽  
Tubular Cells ◽  
Renal Tubular Cells ◽  
P53 Activation ◽  
Induced Apoptosis

Tubular damage by cisplatin leads to acute renal failure, which limits its use in cancer therapy. In tubular cells, a primary target for cisplatin is presumably the genomic DNA. However, the pathway relaying the signals of DNA damage to tubular cell death is unclear. In response to DNA damage, the tumor suppressor gene p53 is induced and is implicated in subsequent DNA repair and cell death by apoptosis. The current study was designed to examine the role of p53 in cisplatin-induced apoptosis in cultured rat kidney proximal tubular cells. Cisplatin at 20 μM induced apoptosis in ∼70% of cells, which was partially suppressed by carbobenzoxy-Val-Ala-Asp-fluoromethyl ketone (VAD), a general caspase inhibitor. Of interest, cisplatin-induced apoptosis was also suppressed by pifithrin-α, a pharmacological inhibitor of p53. Cisplatin-induced caspase activation was completely inhibited by VAD, but only partially by pifithrin-α. Early during cisplatin treatment, p53 was phosphorylated and upregulated. The p53 activation was blocked by pifithrin-α, but not by VAD. Bcl-2 expression abolished cisplatin-induced apoptosis without blocking p53 phosphorylation or induction. The results suggest that p53 activation might be an early signal for apoptosis during cisplatin treatment. To further determine the role of p53, tubular cells were stably transfected with a dominant-negative mutant of p53 with diminished transcriptional activity. Expression of the mutant attenuated cisplatin-induced apoptosis and caspase activation. In conclusion, the results support an important role for p53 in cisplatin-induced apoptosis in renal tubular cells. p53 May regulate apoptosis through the transcription of apoptotic genes.

scholarly journals PTEN Activation by DNA Damage Induces Protective Autophagy in Response to Cucurbitacin B in Hepatocellular Carcinoma Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
Yanan Niu ◽  
Wen Sun ◽  
Jin-Jian Lu ◽  
Dik-Lung Ma ◽  
Chung-Hang Leung ◽  
...  
Keyword(s):  
Dna Damage ◽  
Carcinoma Cells ◽  
Caspase Activation ◽  
Phosphatase And Tensin Homolog ◽  
Cucurbitacin B ◽  
Tensin Homolog ◽  
Phosphorylated Akt ◽  
Protein Expressions ◽  
Ros Formation ◽  
Induced Apoptosis

Cucurbitacin B (Cuc B), a natural product, induced both protective autophagy and DNA damage mediated by ROS while the detailed mechanisms remain unclear. This study explored the mechanism of Cuc B-induced DNA damage and autophagy. Cuc B decreased cell viability in concentration- and time-dependent manners. Cuc B caused long comet tails and increased expression of γ-H2AX, phosphorylation of ATM/ATR, and Chk1/Chk2. Cuc B induced autophagy as evidenced by monodansylcadaverine (MDC) staining, increased expression of LC3II, phosphorylated ULK1, and decreased expression of phosphorylated AKT, mTOR. Cuc B induced apoptosis mediated by Bcl-2 family proteins and caspase activation. Furthermore, Cuc B induced ROS formation, which was inhibited by N-acetyl-L-cysteine (NAC). NAC pretreatment dramatically reversed Cuc B-induced DNA damage, autophagy, and apoptosis. Cuc B-induced apoptosis was reversed by NAC but enhanced by 3-methyladenine (3-MA), chloroquine (CQ), and silencing phosphatase and tensin homolog (PTEN). 3-MA and CQ showed no effect on Cuc B-induced DNA damage. In addition, Cuc B increased PTEN phosphorylation and silence PTEN restored Cuc B-induced autophagic protein expressions without affecting DNA damage. In summary, Cuc B induced DNA damage, apoptosis, and protective autophagy mediated by ROS. PTEN activation in response to DNA damage bridged DNA damage and prosurvival autophagy.

Thymoquinone sensitizes human hepatocarcinoma cells to TRAIL-induced apoptosis via oxidative DNA damage

DNA Repair ◽  
2021 ◽  
pp. 103117
Author(s):  
Ruikui Zhang ◽  
Tao Wu ◽  
Peipei Zheng ◽  
Ming Liu ◽  
Guixiang Xu ◽  
...  
Keyword(s):  
Dna Damage ◽  
Oxidative Dna Damage ◽  
Hepatocarcinoma Cells ◽  
Induced Apoptosis ◽  
Human Hepatocarcinoma Cells

scholarly journals Inhibition of histone methyltransferase G9a attenuates liver cancer initiation by sensitizing DNA-damaged hepatocytes to p53-induced apoptosis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Takuma Nakatsuka ◽  
Keisuke Tateishi ◽  
Hiroyuki Kato ◽  
Hiroaki Fujiwara ◽  
Keisuke Yamamoto ◽  
...  
Keyword(s):  
Dna Damage ◽  
Epigenetic Modification ◽  
Histone Methyltransferase ◽  
Preventive Strategy ◽  
Tumor Initiation ◽  
Liver Transcriptome ◽  
Genetic Abnormalities ◽  
Responsive Element ◽  
Induced Apoptosis

AbstractWhile the significance of acquired genetic abnormalities in the initiation of hepatocellular carcinoma (HCC) has been established, the role of epigenetic modification remains unknown. Here we identified the pivotal role of histone methyltransferase G9a in the DNA damage-triggered initiation of HCC. Using liver-specific G9a-deficient (G9aΔHep) mice, we revealed that loss of G9a significantly attenuated liver tumor initiation caused by diethylnitrosamine (DEN). In addition, pharmacological inhibition of G9a attenuated the DEN-induced initiation of HCC. After treatment with DEN, while the induction of γH2AX and p53 were comparable in the G9aΔHep and wild-type livers, more apoptotic hepatocytes were detected in the G9aΔHep liver. Transcriptome analysis identified Bcl-G, a pro-apoptotic Bcl-2 family member, to be markedly upregulated in the G9aΔHep liver. In human cultured hepatoma cells, a G9a inhibitor, UNC0638, upregulated BCL-G expression and enhanced the apoptotic response after treatment with hydrogen peroxide or irradiation, suggesting an essential role of the G9a-Bcl-G axis in DNA damage response in hepatocytes. The proposed mechanism was that DNA damage stimuli recruited G9a to the p53-responsive element of the Bcl-G gene, resulting in the impaired enrichment of p53 to the region and the attenuation of Bcl-G expression. G9a deletion allowed the recruitment of p53 and upregulated Bcl-G expression. These results demonstrate that G9a allows DNA-damaged hepatocytes to escape p53-induced apoptosis by silencing Bcl-G, which may contribute to the tumor initiation. Therefore, G9a inhibition can be a novel preventive strategy for HCC.

scholarly journals ATR-Chk2 signaling in p53 activation and DNA damage response during cisplatin-induced apoptosis. VOLUME 283 (2008) PAGES 6572-6583

2008 ◽  
Vol 283 (22) ◽  
pp. 15512
Author(s):  
Navjotsingh Pabla ◽  
Shuang Huang ◽  
Qing-Sheng Mi ◽  
Rene Daniel ◽  
Zheng Dong
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Damage Response ◽  
P53 Activation ◽  
Induced Apoptosis

Nuclear translocation of dihydrofolate reductase is not a pre-requisite for DNA damage induced apoptosis

APOPTOSIS ◽  
2009 ◽  
Vol 14 (5) ◽  
pp. 699-710 ◽  
Author(s):  
Ting-Ting Yuan ◽  
Ying Huang ◽  
Ci-Xiang Zhou ◽  
Yun Yu ◽  
Li-Shun Wang ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dihydrofolate Reductase ◽  
Nuclear Translocation ◽  
Induced Apoptosis

scholarly journals Execution of Apoptosis Signal-regulating Kinase 1 (ASK1)-induced Apoptosis by the Mitochondria-dependent Caspase Activation

2000 ◽  
Vol 275 (34) ◽  
pp. 26576-26581 ◽  
Author(s):  
Takiko Hatai ◽  
Atsushi Matsuzawa ◽  
Seiji Inoshita ◽  
Yoshiyuki Mochida ◽  
Takayuki Kuroda ◽  
...  
Keyword(s):  
Caspase Activation ◽  
Induced Apoptosis

scholarly journals Caspase-8 deficiency induces a switch from TLR3 induced apoptosis to lysosomal cell death in neuroblastoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Marie-Anaïs Locquet ◽  
Gabriel Ichim ◽  
Joseph Bisaccia ◽  
Aurelie Dutour ◽  
Serge Lebecque ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Neuroblastoma Cell ◽  
Death Receptor ◽  
Neuroblastoma Cell Line ◽  
Caspase 8 ◽  
Caspase Activation ◽  
Extrinsic Pathway ◽  
Lysosomal Membrane Permeabilization ◽  
Induced Apoptosis

AbstractIn cancer cells only, TLR3 acquires death receptor properties by efficiently triggering the extrinsic pathway of apoptosis with Caspase-8 as apical protease. Here, we demonstrate that in the absence of Caspase-8, activation of TLR3 can trigger a form of programmed cell death, which is distinct from classical apoptosis. When TLR3 was activated in the Caspase-8 negative neuroblastoma cell line SH-SY5Y, cell death was accompanied by lysosomal permeabilization. Despite caspases being activated, lysosomal permeabilization as well as cell death were not affected by blocking caspase-activity, positioning lysosomal membrane permeabilization (LMP) upstream of caspase activation. Taken together, our data suggest that LMP with its deadly consequences represents a “default” death mechanism in cancer cells, when Caspase-8 is absent and apoptosis cannot be induced.

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