scholarly journals Urea transport B gene induces melanoma B16 cell death via activation of p53 and mitochondrial apoptosis

2018 ◽  
Vol 109 (12) ◽  
pp. 3762-3773 ◽  
Author(s):  
Lianqin Liu ◽  
Yuxin Sun ◽  
Yunxia Zhao ◽  
Qian Wang ◽  
Hua Guo ◽  
...  
Keyword(s):  
Cell Death ◽  
Mitochondrial Apoptosis ◽  
Urea Transport ◽  
Melanoma B16

The novel dual BET/HDAC inhibitor TW09 mediates cell death by mitochondrial apoptosis in rhabdomyosarcoma cells

2020 ◽  
Vol 486 ◽  
pp. 46-57 ◽  
Author(s):  
Stephanie Laszig ◽  
Cathinka Boedicker ◽  
Tim Weiser ◽  
Stefan Knapp ◽  
Simone Fulda
Keyword(s):  
Cell Death ◽  
Hdac Inhibitor ◽  
The Novel ◽  
Mitochondrial Apoptosis

scholarly journals TrxR2 overexpression alleviates inflammation-mediated neuronal death via reducing the oxidative stress and activating the Akt–Parkin pathway

2019 ◽  
Vol 8 (5) ◽  
pp. 641-653 ◽  
Author(s):  
Jinbao Gao ◽  
Yunjun Li ◽  
Wende Li ◽  
Haijiang Wang
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Cell Viability ◽  
Western Blotting ◽  
Neuronal Death ◽  
Protective Effects ◽  
Mitochondrial Apoptosis ◽  
Inflammation Response ◽  
N2a Cells

Abstract Neuronal death caused by inflammatory cytokine-mediated neuroinflammation is being extensively explored. Thioredoxin reductase (TrxR) 2 is a novel mediator of inflammation response. In the current study, we focus on the mechanisms of TrxR2 overexpression in inflammation-mediated neuronal death. LPS was used to induce neuroinflammation in N2a cells in vitro. Adenovirus-loaded TrxR2 was transfected into N2a cells to up-regulate TrxR2 expression. Then, cell viability was determined via MTT assay and TUNEL assay. Apoptosis was measured via western blotting and ELISA. Oxidative stress was detected via ELISA and flow cytometry. A pathway inhibitor was used to verify the role of the Akt–Parkin pathway in the LPS-mediated N2a cell death in the presence of TrxR2 overexpression. With the help of immunofluorescence assay and western blotting, we found that TrxR2 expression was significantly reduced in response to LPS treatment, and this effect was associated with N2a cell death via apoptosis. At the molecular level, TrxR2 overexpression elevated the activity of the Akt–Parkin pathway, as evidenced by the increased expression of p-Akt and Parkin. Interestingly, inhibition of the Akt–Parkin pathway abolished the regulatory effect of TrxR2 on LPS-treated N2a cells, as evidenced by the decreased cell viability and increased apoptotic ratio. Besides, TrxR2 overexpression also reduced oxidative stress, inflammation factor transcription and mitochondrial apoptosis. However, inhibition of Akt–Parkin axis abrogated the protective effects of TrxR2 on redox balance, mitochondrial performance and cell survival. LPS-mediated neuronal death was linked to a drop in TrxR2 overexpression and the inactivation of the Akt–Parkin pathway. Overexpression of TrxR2 sustained mitochondrial function, inhibited oxidative stress, repressed inflammation response, and blocked mitochondrial apoptosis, finally sending a pro-survival signal for the N2a cells in the setting of LPS-mediated inflammation environment.

scholarly journals Novel camphor-based pyrimidine derivatives induced cancer cell death through a ROS-mediated mitochondrial apoptosis pathway

RSC Advances ◽  
2019 ◽  
Vol 9 (51) ◽  
pp. 29711-29720
Author(s):  
Yan Zhang ◽  
Yunyun Wang ◽  
Yuxun Zhao ◽  
Wen Gu ◽  
Yongqiang Zhu ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cell ◽  
Mitochondrial Apoptosis ◽  
Pyrimidine Derivatives ◽  
Apoptosis Pathway ◽  
Mitochondrial Apoptosis Pathway ◽  
Cancer Cell Death ◽  
Anti Tumor Activity

A series of novel camphor-based pyrimidine derivatives were synthesized and characterized. We found the compound 3f exhibited strongest anti-tumor activity via ROS-mediated mitochondrial apoptosis pathway.

scholarly journals Prototheca zopfiiGenotype II induces mitochondrial apoptosis in models of bovine mastitis

2019 ◽  
Author(s):  
Muhammad Shahid ◽  
Eduardo R. Cobo ◽  
Liben Chen ◽  
Paloma A. Cavalcante ◽  
Herman W. Barkema ◽  
...  
Keyword(s):  
Cell Death ◽  
Mammary Gland ◽  
Epithelial Cells ◽  
Mammary Epithelial Cells ◽  
Bovine Mastitis ◽  
Mammary Epithelial ◽  
Mitochondrial Apoptosis ◽  
Prototheca Zopfii ◽  
Severe Inflammation ◽  
Mammary Tissues

AbstractPrototheca zopfiiis an alga increasingly isolated from bovine mastitis. Of the two genotypes ofP. zopfii(genotype I and II (GT-I and II)),P. zopfiiGT-II is the genotype associated with acute mastitis and decreased milk production by unknown mechanisms. The objective was to determine inflammatory and apoptotic roles ofP. zopfiiGT-II in cultured mammary epithelial cells (from cattle and mice) and murine macrophages and using a murine model of mastitis.Prototheca zopfiiGT-II (but not GT-I) invaded bovine and murine mammary epithelial cells (MECs) and induced apoptosis, as determined by the terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labeling assay. ThisP. zopfiiGT-II driven apoptosis corresponded to mitochondrial pathways; mitochondrial transmembrane resistance (ΔΨm) was altered and modulation of mitochondrion-mediated apoptosis regulating genes changed (increased transcriptionalBax, cytochrome-c andApaf-1and downregulatedBcl-2), whereas caspase-9 and -3 expression increased. Apoptotic effects byP. zopfiiGT-II were more pronounced in macrophages compared to MECs. In a murine mammary infection model,P. zopfiiGT-II replicated in the mammary gland and caused severe inflammation with infiltration of macrophages and neutrophils and upregulation of pro-inflammatory genes (TNF-α,IL-1βandCxcl-1) and also apoptosis of epithelial cells. Thus, we concludedP. zopfiiGT-II is a mastitis-causing pathogen that triggers severe inflammation and also mitochondrial apoptosis.Author summaryBovine mastitis (inflammation of the udder) reduces milk production and quality, causing huge economic losses in the dairy industry worldwide. Although the algaPrototheca zopfiiis a major cause of mastitis in dairy cows, mechanisms by which it damages mammary tissues are not well known. Here, we used cell cultures and a mouse model of mastitis to determine howProtothecacaused inflammation and cell death in mammary tissues.Protothecainvaded mammary gland cells, from cattle and mice, as well as macrophages (white cells that take up and kill pathogens) and caused cell death by interfering with mitochondria. Furthermore,Protothecacauses severe inflammation and tissue damage when injected into the mammary glands of mice. Although there are two genotypes ofP. zopfii, only genotype II causes tissue damage, whereas gentotype I, common in farm environments, does not damage mammary tissues. SinceP. zopfiiis an alga and not a bacterium, antibiotic treatments, frequently used to treat mastitis in cattle, are not effective against this organism. Understanding howP. zopfiidamages mammary tissue and causes mastitis is important new knowledge to promote future development of evidence-based approaches to prevent and treat mammary gland infections with this organism.

scholarly journals Zirconia Nanoparticles Induce HeLa Cell Death Through Mitochondrial Apoptosis and Autophagy Pathways Mediated by ROS

2021 ◽  
Vol 9 ◽  
Author(s):  
Yinghui Shang ◽  
Qinghai Wang ◽  
Jian Li ◽  
Haiting Liu ◽  
Qiangqiang Zhao ◽  
...  
Keyword(s):  
Cell Death ◽  
Hela Cell ◽  
Hela Cells ◽  
Mitochondrial Apoptosis ◽  
Ki 67 ◽  
Transmission Electron ◽  
Anti Tumor Activity ◽  
Zirconia Nanoparticles

Zirconia nanoparticles (ZrO2 NPs) are commonly used in the field of biomedical materials, but their antitumor activity and mechanism is unclear. Herein, we evaluated the anti-tumor activity of ZrO2 NPs and explored the anti-tumor mechanism. The results of in vitro and in vivo experiments showed that the level of intracellular reactive oxygen species (ROS) in HeLa cells was elevated after ZrO2 NPs treatment. Transmission electron microscopy (TEM) showed that after treatment with ZrO2 NPs, the mitochondria of HeLa cells were swollen, accompanied with the induction of autophagic vacuoles. In addition, flow cytometry analysis showed that the apoptotic rate of HeLa cells increased significantly by Annexin staining after treatment with ZrO2 NPs, and the mitochondrial membrane potential (MMP) was reduced significantly. The proliferation of HeLa cells decreased as indicated by reduced Ki-67 labeling. In contrast, TUNEL-positive cells in tumor tissues increased after treatment with ZrO2 NPs, which is accompanied by increased expression of mitochondrial apoptotic proteins including Bax, Caspase-3, Caspase-9, and Cytochrome C (Cyt C) and increased expression of autophagy-related proteins including Atg5, Atg12, Beclin-1, and LC3-II. Treating HeLa cells with N-acetyl-L-cysteine (NAC) significantly reduced ROS, rate of apoptosis, MMP, and in vivo anti-tumor activity. In addition, apoptosis- and autophagy-related protein expressions were also suppressed. Based on these observations, we conclude that ZrO2 NPs induce HeLa cell death through ROS mediated mitochondrial apoptosis and autophagy.

scholarly journals Intracellular expression of arginine deiminase activates the mitochondrial apoptosis pathway by inhibiting cytosolic ferritin and inducing chromatin autophagy

2020 ◽  
Author(s):  
Qingyuan Feng ◽  
Xuzhao Bian ◽  
Xuan Liu ◽  
Ying Wang ◽  
Huiting Zhou ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Western Blotting ◽  
Mitochondrial Damage ◽  
Arginine Deiminase ◽  
Immunofluorescent Staining ◽  
Mitochondrial Apoptosis ◽  
Apoptosis Pathway ◽  
P53 Expression ◽  
Mitochondrial Apoptosis Pathway

Abstract Background: Based on its low toxicity, arginine starvation therapy has the potential to cure malignant tumors that cannot be treated surgically. The Arginine deiminase (ADI) gene has been identified to be an ideal cancer-suppressor gene. ADI expressed in the cytosol displays higher oncolytic efficiency than ADI-PEG20 (Pegylated Arginine Deiminase by PEG 20,000). However, it is still unknown whether cytosolic ADI has the same mechanism of action as ADI-PEG20 or other underlying cellular mechanisms. Methods: The interactions of ADI with other protein factors were screened by yeast hybrids, and verified by co-immunoprecipitation and immunofluorescent staining. The effect of ADI inhibiting the ferritin light-chain domain (FTL) in mitochondrial damage was evaluated by site-directed mutation and flow cytometry. Control of the mitochondrial apoptosis pathway was analyzed by Western Blotting and real-time PCR experiments. The effect of p53 expression on cancer cells death was assessed by siTP53 transfection. Chromatin autophagy was explored by immunofluorescent staining and Western Blotting. Results: ADI expressed in the cytosol inhibited the activity of cytosolic ferritin by interacting with FTL. The inactive mutant of ADI still induced apoptosis in certain cell lines of ASS- through mitochondrial damage. Arginine starvation also generated an increase in the expression of p53 and p53AIP1, which aggravated the cellular mitochondrial damage. Chromatin autophagy appeared at a later stage of arginine starvation. DNA damage occurred along with the entire arginine starvation process. Histone 3 (H3) was found in autophagosomes, which implies that cancer cells attempted to utilize the arginine present in histones to survive during arginine starvation. Conclusions: Mitochondrial damage is the major mechanism of cell death induced by cytosolic ADI. The process of chromatophagy does not only stimulate cancer cells to utilize histone arginine but also speeds up cancer cell death at a later stage of arginine starvation.

scholarly journals Berberine induces autophagic cell death and mitochondrial apoptosis in liver cancer cells: The cellular mechanism

2010 ◽  
Vol 111 (6) ◽  
pp. 1426-1436 ◽  
Author(s):  
Ning Wang ◽  
Yibin Feng ◽  
Meifen Zhu ◽  
Chi-Man Tsang ◽  
Kwan Man ◽  
...  
Keyword(s):  
Cell Death ◽  
Liver Cancer ◽  
Cancer Cells ◽  
Cellular Mechanism ◽  
Autophagic Cell Death ◽  
Mitochondrial Apoptosis ◽  
Liver Cancer Cells

Endoplasmic reticulum stress mediated the xanthohumol induced murine melanoma B16-F10 cell death

2019 ◽  
Vol 22 (9) ◽  
pp. 850-863
Author(s):  
Yi-Ming Zhang ◽  
Xiao-Bing Shi ◽  
Bo Xu ◽  
Cheng-Shan Yuan ◽  
Wei Zheng ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Endoplasmic Reticulum Stress ◽  
Murine Melanoma ◽  
Melanoma B16
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