scholarly journals Potential involvement of F0F1-ATP(synth)ase and reactive oxygen species in apoptosis induction by the antineoplastic agent erucylphosphohomocholine in glioblastoma cell lines

APOPTOSIS ◽  
2010 ◽  
Vol 15 (7) ◽  
pp. 753-768 ◽  
Author(s):  
Leo Veenman ◽  
Julia Alten ◽  
Karen Linnemannstöns ◽  
Yulia Shandalov ◽  
Sivan Zeno ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Lines ◽  
Antineoplastic Agent ◽  
Reactive Oxygen ◽  
Glioblastoma Cell ◽  
Oxygen Species ◽  
Apoptosis Induction ◽  
Glioblastoma Cell Lines

scholarly journals Antimicrobial Peptide TP4 Induces ROS-Mediated Necrosis by Triggering Mitochondrial Dysfunction in Wild-Type and Mutant p53 Glioblastoma Cells

Cancers ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 171 ◽  
Author(s):  
Bor-Chyuan Su ◽  
Chieh-Yu Pan ◽  
Jyh-Yih Chen
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Dna Damage ◽  
Reactive Oxygen ◽  
Mutant P53 ◽  
Glioblastoma Cell ◽  
Oxygen Species ◽  
Wild Type ◽  
Glioblastoma Cells ◽  
Glioblastoma Cell Lines

Antimicrobial peptide tilapia piscidin 4 (TP4) from Oreochromis niloticus exhibits potent bactericidal and anti-tumorigenic effects. In a variety of cancers, the mutation status of p53 is a decisive factor for therapeutic sensitivity. Therefore, we investigated the impact of p53 status on TP4-induced cytotoxicity in glioblastoma cell lines and the molecular mechanisms that govern cytotoxic effects. Both U87MG (wild-type/WT p53) and U251 (mutant p53) glioblastoma cell lines were sensitive to TP4-induced cytotoxicity. The necrosis inhibitors Necrostatin-1 and GSK’872 attenuated TP4-induced cytotoxicity, and TP4 treatment induced the release of cyclophilin A, a biomarker of necrosis. Moreover, TP4 induced mitochondrial hyperpolarization and dysfunction, which preceded the elevation of intracellular reactive oxygen species, DNA damage, and necrotic cell death in both U87MG and U251 glioblastoma cells. p38 was also activated by TP4, but did not contribute to cytotoxicity. SB202190, a specific p38 inhibitor, enhanced TP4-induced oxidative stress, mitochondrial dysfunction, and cytotoxicity, suggesting a protective role of p38. Furthermore, TP4-induced cytotoxicity, oxidative stress, phosphorylation of p38, and DNA damage were all attenuated by the mitochondrial-targeted reactive oxygen species (ROS) scavenger MitoTEMPO, or the reactive oxygen species scavenger N-acetyl-L-cysteine. Based on these data, we conclude that TP4 induces necrosis in both WT and mutant p53 glioblastoma cells through a mitochondrial ROS-dependent pathway.

scholarly journals Role of Resveratrol in Transmitochondrial AMD RPE Cells

Nutrients ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 159
Author(s):  
Sonali Nashine ◽  
Anthony B. Nesburn ◽  
Baruch D. Kuppermann ◽  
Maria Cristina Kenney
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Viability ◽  
Macular Degeneration ◽  
Cell Lines ◽  
Blood Platelets ◽  
Reactive Oxygen ◽  
Age Related Macular Degeneration ◽  
Oxygen Species ◽  
Positive Effects ◽  
Patient Cell

Resveratrol is a phytoalexin, stilbenoid compound with antioxidant properties attributable to its bioactive trans-resveratrol content. This study characterized the effects of over-the-counter (OTC) resveratrol nutritional supplements and a HPLC-purified resveratrol formulation, in human transmitochondrial age-related macular degeneration (AMD) retinal pigment epithelial (RPE) patient cell lines. These cell lines, which were created by fusing blood platelets obtained from dry and wet AMD patients with mitochondria-deficient (Rho0) ARPE-19 cells, had identical nuclei (derived from ARPE-19 cells) but different mitochondria that were derived from AMD patients. After resveratrol treatment, the levels of cell viability and reactive oxygen species production were measured. Results demonstrated that treatment with different resveratrol formulations improved cell viability and decreased reactive oxygen species generation in each AMD patient cell line. Although further studies are required to establish the cytoprotective potential of resveratrol under different physiological conditions, this novel study established the positive effects of OTC resveratrol supplements in macular degeneration patient cybrid cell lines in vitro.

scholarly journals Snake venom causes apoptosis by increasing the reactive oxygen species in colorectal and breast cancer cell lines

2016 ◽  
Vol Volume 9 ◽  
pp. 6485-6498 ◽  
Author(s):  
Abdulrahman Al-Asmari ◽  
Riyasdeen Anvarbatcha ◽  
Mohammad Al-Shahrani ◽  
Mozaffarul Islam
Keyword(s):  
Breast Cancer ◽  
Reactive Oxygen Species ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Snake Venom ◽  
Reactive Oxygen ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Oxygen Species

GNG11 (G-protein subunit γ 11) suppresses cell growth with induction of reactive oxygen species and abnormal nuclear morphology in human SUSM-1 cells

2017 ◽  
Vol 95 (4) ◽  
pp. 517-523 ◽  
Author(s):  
Yuki Takauji ◽  
Ikuru Kudo ◽  
Atsuki En ◽  
Ryo Matsuo ◽  
Mohammad Nazir Hossain ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
G Protein ◽  
Cell Lines ◽  
Hela Cells ◽  
Reactive Oxygen ◽  
Ros Generation ◽  
Nuclear Morphology ◽  
Oxygen Species ◽  
Protein Subunit ◽  
Regulatory Relationship

Enforced expression of GNG11, G-protein subunit γ 11, induces cellular senescence in normal human diploid fibroblasts. We here examined the effect of the expression of GNG11 on the growth of immortalized human cell lines, and found that it suppressed the growth of SUSM-1 cells, but not of HeLa cells. We then compared these two cell lines to understand the molecular basis for the action of GNG11. We found that expression of GNG11 induced the generation of reactive oxygen species (ROS) and abnormal nuclear morphology in SUSM-1 cells but not in HeLa cells. Increased ROS generation by GNG11 would likely be caused by the down-regulation of the antioxidant enzymes in SUSM-1 cells. We also found that SUSM-1 cells, even under normal culture conditions, showed higher levels of ROS and higher incidence of abnormal nuclear morphology than HeLa cells, and that abnormal nuclear morphology was relevant to the increased ROS generation in SUSM-1 cells. Thus, SUSM-1 and HeLa cells showed differences in the regulation of ROS and nuclear morphology, which might account for their different responses to the expression of GNG11. Thus, SUSM-1 cells may provide a unique system to study the regulatory relationship between ROS generation, nuclear morphology, and G-protein signaling.

Mimosine Induces Apoptosis through Metal Ion Chelation, Mitochondrial Activation and Reactive Oxygen Species Production in Human Leukemic Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4481-4481 ◽  
Author(s):  
Maher Hallak ◽  
Alexander Dvilansky ◽  
Ofer Shpilberg ◽  
Itai Levi ◽  
Julia Mazar ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Lines ◽  
Metal Ion ◽  
Reactive Oxygen Species Production ◽  
Reactive Oxygen ◽  
G1 Arrest ◽  
Oxygen Species ◽  
Effect Of Mimosine ◽  
Apoptotic Effect ◽  
Species Production

Abstract Mimosine, a non-protein amino acid, acts as a reversible inhibitor of DNA replication, and is widely used to synchronize cells at G1 phase of the cell cycle. We tested the possibility that mimosine might have an apoptotic effect on two types of AML cells: the monoblastic U-937 and the promyelocytic HL-60 cell lines. We show that mimosine induces apoptosis in both cell lines, with U-937 cells being more sensitive. The apoptotic effect of mimosine was antagonized by the addition of exogenous iron, indicating that it may act through iron chelation. Its mode of action was thus compared to that of desferrioxamine (DFO), a therapeutic iron chelating agent. Mimosine and DFO differed in their sensitivity to the suppressive effect of exogenous sources of iron in the form of hemin and ferrous sulfate suggesting different targets of action. Addition of another metal ion cupric sulfate was also able to antagonize the apoptotic effect of mimosine, undermining the notion that apoptosis is mediated through inhibition of ribonucleotide reductase, since this enzyme is solely dependent on iron for its activity. Moreover, when higher concentrations of iron were added to mimosine, cell death shifted from apoptosis to necrosis. Induction of apoptosis by both mimosine and DFO caused an early reduction in mitochondrial transmembrane potential and increase in caspase-3 activity, while only mimosine induced oxidative stress. In summary, our results imply that besides its known effect on DNA synthesis and G1 arrest, mimosine also activates apoptosis through an intrinsic pathway as well as reactive oxygen species production and thus elicits its anticancer effect by multiple pathways.

Histone Deacetylase Inhibitor (HDACi) PCI-24781 and Bortezomib Result in Synergistic Apoptosis in Hodgkin Lymphoma (HL) and Non-Hodgkin’s Lymphoma (NHL) Cell Lines: Investigation of Cell Death and NFKB-Mediated Pathways.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3589-3589 ◽  
Author(s):  
Savita Bhalla ◽  
Kevin David ◽  
Lauren Mauro ◽  
Sheila Prachand ◽  
Mint Sirisawad ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Cell Lines ◽  
Reactive Oxygen ◽  
Fold Increase ◽  
Oxygen Species ◽  
Minimal Cell ◽  
Histone 3 ◽  
Dichlorofluorescein Diacetate ◽  
20 Nm

Abstract HDACi block cancer cell proliferation by mechanisms that involve epigenetic gene regulation leading to cell growth arrest, differentiation, and apoptosis. Bortezomib inhibits NFKB signaling and induces apoptosis. Furthermore, anti-tumor activity of HDACi and bortezomib both depend in part on reactive oxygen species (ROS)-mediated pathways. Both have activity in NHL. We reasoned that these agents may be synergistic in part due to their dependence on overlapping pathways. We investigated the biology of PCI-24781, a pan-HDACi currently in clinical trials, and bortezomib both alone, and in combination, in HL (L428) and NHL cell lines (HF1, Ramos, & SUDHL4). Cells were incubated with increasing concentrations of PCI-24781 and bortezomib (0.25–2.0μM and 2.5–20nM, respectively) for 24–72 hour (hr). Apoptosis was determined by fluorescence-activated cell sorting (FACS) using AnnexinV-FITC/propidium iodide (AnnexinV+/PI+) staining. Reactive oxygen species (ROS) were measured by oxidation of 2′7′dichlorofluorescein diacetate (H2DCFDA) to DCF and detected by FACS. Downstream targets of NFKB such as NFKB1, Myc and IL-8 were measured in Ramos using quantitative real time polymerase chain reaction (RT-PCR) following 24 hr incubation of cells with PCI-24781 and bortezomib alone, and in combination. Dose-dependent apoptosis was seen with PCI-24781 and bortezomib alone in all HL and NHL cell lines. IC70 (dose to achieve 70% AnnexinV+/PI+) was 1μM for PCI-24781 and 2μM for L428. With bortezomib, the IC50 was 10nM in Ramos, HF1, and SUDHL4 and 20 nM in L428. The combination of PCI-24781 and bortezomib resulted in synergistic apoptosis (combination index <0.2) in all 3 NHL cell lines (IC80=0.25μM PCI-24781/5nM bortezomib) and L428 (IC80=0.5μM PCI-24781/10nM bortezomib) compared with minimal cell death using each agent alone at those concentrations. Furthermore, immunoblots of L428 and Ramos showed enhanced caspase 3 and caspase 8 cleavage with the combination of PCI-24781 and bortezomib compared to either agent alone, suggesting that the synergy seen was in part caspase-dependent. HL and NHL cell lines showed a 3- to 4-fold increase in ROS with PCI-24781 or bortezomib alone and in combination at 24hr. Moreover, we found that hyperacetylation of histone-3 and histone-4 on immunoblots of cells treated with combination PCI-2478/bortezomib was significantly increased compared to PCI-24781 alone. Finally, we found that in Ramos cells PC-24781/bortezomib together resulted in downregulation of NFKB targets NFKB1 and Myc, but not IL-8. We conclude that PCI-24781 and bortezomib are active in lymphoma cell lines and that the combination results in synergistic apoptosis. Apoptosis was accompanied by caspase activation and synergistic downregulation of the NFkB pathway. These data have important clinical implications for NHL and HL.

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