Reactive oxygen species and Ca2+ are involved in cadmium-induced cell killing in yeast cells

Cadmium (Cd) is one of the most toxic heavy metals. It is of great environmental concern and its toxicity has been investigated in a variety of cells. In this study, we elucidated the toxic effects of Cd in cells of yeast (Saccharomyces cerevisiae). Our results showed that Cd2+ (0.05–5.0 mmol·L−1) significantly inhibited yeast cell growth, and the inhibitory effect was positively correlated with Cd2+ concentrations. Cd2+ caused loss of yeast cell viability in a concentration- and duration-dependent manner. Intracellular reactive oxygen species (ROS) and Ca2+ levels increased in yeast cells after exposure to 5.0 mmol·L−1 Cd for 6 h. Cd2+-caused cell viability loss was blocked by antioxidants (0.5 mmol·L−1 ascorbic acid or 500 U·mL−1 catalase) or Ca2+ antagonists (0.5 mmol·L−1 ethylene glycol tetraacetic acid or 0.5 mmol·L−1 LaCl3). Moreover, a collapse of mitochondrial membrane potential (ΔΨm) was observed in Cd2+-treated yeast cells. These results indicate that Cd-induced yeast cell killing was associated with the elevation of intracellular ROS and Ca2+ levels and also the loss of ΔΨm.

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Reactive oxygen species and Ca2+are involved in sodium arsenite-induced cell killing in yeast cells

FEMS Microbiology Letters ◽

10.1111/1574-6968.12131 ◽

2013 ◽

Vol 343 (1) ◽

pp. 57-63 ◽

Cited By ~ 4

Author(s):

Lihua Wu ◽

Huilan Yi ◽

Hufang Zhang

Keyword(s):

Reactive Oxygen Species ◽

Sodium Arsenite ◽

Reactive Oxygen ◽

Cell Killing ◽

Yeast Cells ◽

Oxygen Species

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Pandanus conoideus Lamk Oil Protects Against Inflammation Through Regulating Reactive Oxygen Species in LPS-Induced Murine Macrophages

Natural Product Communications ◽

10.1177/1934578x20953664 ◽

2020 ◽

Vol 15 (9) ◽

pp. 1934578X2095366

Author(s):

Yun-Hee Rhee ◽

Ye Kyu Park ◽

Jong-Soo Kim

Keyword(s):

Reactive Oxygen Species ◽

Cell Viability ◽

Reactive Oxygen ◽

Enzyme Linked Immunosorbent Assay ◽

Prostaglandin E ◽

Raw 264.7 ◽

Dependent Manner ◽

Oxygen Species ◽

Anti Inflammatory ◽

Leading Compounds

The aim of this study was to investigate the anti-inflammatory properties of Pandanus conoideus Lamk (red fruit oil [RFO]) and establish the signal pathway of the leading compounds. RAW 264.7 murine macrophage cells were used with lipopolysaccharide (LPS). Cell viability and the pro-inflammatory factors were investigated using MTT assay, real-time polymerase chain reaction (PCR), western blot analysis, and enzyme-linked immunosorbent assay. The quantification of leading compounds in RFO was performed using high-performance liquid chromatography (HPLC). RFO did not reduce RAW 264.7 cell viability. RFO significantly reduced the production of nitric oxide (NO), cyclooxygenase-2, and prostaglandin E2, and both the protein level and mRNA level of inducible NO synthase in LPS-induced macrophages. RFO also regulated the reactive oxygen species (ROS) in LPS-induced macrophages. RFO attenuated the translocation of the nuclear factor κB (NF-κB) p65 subunit, phosphorylation of I-κB, p38, extracellular signal-regulated kinase, and c-Jun N-terminal kinase (JNK) in a dose-dependent manner. HPLC analysis determined that 1 g of RFO had 14.05 ± 0.8 mg of β-cryptoxanthin and 7.4 ± 0.7 mg of β-carotene. In conclusion, RFO provides an anti-inflammatory effect by regulating ROS and NF-κB through mitogen-activated protein kinase due to antioxidant activity.

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Iron overload induced by ferric ammonium citrate triggers reactive oxygen species-mediated apoptosis via both extrinsic and intrinsic pathways in human hepatic cells

Human & Experimental Toxicology ◽

10.1177/0960327115597312 ◽

2015 ◽

Vol 35 (6) ◽

pp. 598-607 ◽

Cited By ~ 13

Author(s):

S-W Li ◽

C-M Liu ◽

J Guo ◽

AM Marcondes ◽

J Deeg ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Iron Overload ◽

Cell Viability ◽

Signaling Pathway ◽

Reactive Oxygen ◽

Ammonium Citrate ◽

Ferric Ammonium Citrate ◽

Dependent Manner ◽

Oxygen Species ◽

Ferric Ammonium

Background: Hepatic iron overload is common in patients with myelodysplastic syndromes undergoing hematopoietic cell transplantation (HCT) and may predispose to peri- and post-HCT toxicity. To better understand the mechanisms of iron overload-induced liver injury, we examined the effects of iron overload induced by ferric ammonium citrate (FAC) on oxidative stress and apoptosis signaling pathway in human hepatic cell line HH4. Methods and Results: Hepatic HH4 cells were exposed to FAC to force iron uptake, and cellular responses were determined. Incubation with 5 mM FAC resulted in increased intracellular iron content in a time-dependent manner. High concentration of FAC impaired cell viability and increased level of reactive oxygen species (ROS), and addition of antioxidant reagent such as glutathione or N-acetylcysteine dramatically reduced FAC-induced intracellular ROS generation. FAC overload significantly increased the phosphorylation of inhibitor of κB-α, p38 mitogen-activated protein kinase (MAPK), and nuclear factor κ light chain enhancer of activated B cells (NF-κB) p65 and promoted the nuclear translocation of NF-κB p65. Knockdown of Fas and Bid expression by small interfering RNA in iron-treated HH4 cells resulted in restoration of cell viability. Conclusions: We reported that FAC treatment is capable of inducing both extrinsic death receptor and intrinsic mitochondrial signaling pathway-mediated HH4 cells apoptosis through ROS-activated p38 MAPK and NF-κB pathways.

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Induction of Apoptosis in HepaRG Cell Line by Aloe-Emodin through Generation of Reactive Oxygen Species and the Mitochondrial Pathway

Cellular Physiology and Biochemistry ◽

10.1159/000477886 ◽

2017 ◽

Vol 42 (2) ◽

pp. 685-696 ◽

Cited By ~ 31

Author(s):

Xiaoxv Dong ◽

Jing Fu ◽

Xingbin Yin ◽

Changhai Qu ◽

Chunjing Yang ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Cell Viability ◽

Reactive Oxygen ◽

Mitochondrial Pathway ◽

Phase Cell ◽

Dependent Manner ◽

Oxygen Species ◽

Heparg Cell Line ◽

Heparg Cells ◽

Aloe Emodin

Background/Aims: Aloe-emodin (1,8-dihydroxy-3-hydroxymethyl-anthraquinone), an anthraquinone active compounds, is isolated from some traditional medicinal plants such as Rheum palmatum L. and Cassia occidentalis, which induce hepatotoxicity in rats. The aim of this study was to determine potential cytotoxic effects of aloe-emodin on HepaRG cells and to define the underlying mechanism. Methods: MTT was used to evaluate cell viability. Apoptotic cell death was analyzed via Annexin V-FITC/PI double staining. Intracellular reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were determined by flow cytometry, while the expression of apoptosis-related proteins was determined by Western blot analysis. Results: Treatment with aloe-emodin significantly reduced cell viability and induced apoptosis in HepaRG cells in a dose- and time-dependent manner. It provoked ROS generation and depolarization of MMP in HepaRG cells when compared with controls. Aloe-emodin dose-dependently increased release of mitochondrial cytochrome c, and levels of Fas, p53, p21, Bax/Bcl-2 ratio, as well as activation of caspase-3, caspase-8, caspase-9, and subsequent cleavage of poly(ADP-ribose)polymerase (PARP). It also induced S-phase cell cycle arrest by increasing the expression of p21 and cyclin E proteins while significantly decreasing the expression of cyclin A and CDK2. Conclusion: These results suggest that aloe-emodin inhibits cell proliferation and induces apoptosis in HepaRG cells, most probably through a mechanism involving both Fas death pathway and the mitochondrial pathway by generation of ROS. These findings underscore the need for risk assessment of human exposure to aloe-emodin.

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Reactive Oxygen Species-Mediated Autophagy by Ursolic Acid Inhibits Growth and Metastasis of Esophageal Cancer Cells

International Journal of Molecular Sciences ◽

10.3390/ijms21249409 ◽

2020 ◽

Vol 21 (24) ◽

pp. 9409

Author(s):

Na-Ri Lee ◽

Ruo Yu Meng ◽

So-Young Rah ◽

Hua Jin ◽

Navin Ray ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Cell Viability ◽

Ursolic Acid ◽

Reactive Oxygen ◽

Dependent Manner ◽

Oxygen Species ◽

Cell Viability Assay ◽

Protein Levels ◽

Lc3 Puncta ◽

Dose Dependent

Ursolic acid (UA) possesses various pharmacological activities, such as antitumorigenic and anti-inflammatory effects. In the present study, we investigated the mechanisms underlying the effects of UA against esophageal squamous cell carcinoma (ESCC) (TE-8 cells and TE-12 cells). The cell viability assay showed that UA decreased the viability of ESCC in a dose-dependent manner. In the soft agar colony formation assay, the colony numbers and size were reduced in a dose-dependent manner after UA treatment. UA caused the accumulation of vacuoles and LC3 puncta, a marker of autophagosome, in a dose-dependent manner. Autophagy induction was confirmed by measuring the expression levels of LC3 and p62 protein in ESCC cells. UA increased LC3-II protein levels and decreased p62 levels in ESCC cells. When autophagy was hampered using 3-methyladenine (3-MA), the effect of UA on cell viability was reversed. UA also significantly inhibited protein kinase B (Akt) activation and increased p-Akt expression in a dose-dependent manner in ESCC cells. Accumulated LC3 puncta by UA was reversed after wortmannin treatment. LC3-II protein levels were also decreased after treatment with Akt inhibitor and wortmannin. Moreover, UA treatment increased cellular reactive oxygen species (ROS) levels in ESCC in a time- and dose-dependent manner. Diphenyleneiodonium (an ROS production inhibitor) blocked the ROS and UA induced accumulation of LC3-II levels in ESCC cells, suggesting that UA-induced cell death and autophagy are mediated by ROS. Therefore, our data indicate that UA inhibits the growth of ESCC cells by inducing ROS-dependent autophagy.

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Shikonin Induced Program Cell Death through Generation of Reactive Oxygen Species in Renal Cancer Cells

Antioxidants ◽

10.3390/antiox10111831 ◽

2021 ◽

Vol 10 (11) ◽

pp. 1831

Author(s):

Ming-Feng Tsai ◽

Shih-Ming Chen ◽

Ann-Zhi Ong ◽

Yi-Hsuan Chung ◽

Pei-Ni Chen ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Cell Proliferation ◽

Cell Death ◽

Cell Viability ◽

Renal Cancer ◽

Reactive Oxygen ◽

Treated Group ◽

Dependent Manner ◽

Oxygen Species ◽

Acridine Orange Staining

Shikonin mitigated tumor cell proliferation by elevating reactive oxygen species (ROS) levels. Herein, we investigated the effects of shikonin on renal cancer cell (RCC) cell proliferation. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay indicated that shikonin dose-dependently reduced the proliferation of Caki-1 and ACHN cells. Shikonin remarkably triggered necrosis and apoptosis in Caki-1 and ACHN cells in proportion to its concentration. Moreover, necrostatin-1 recovered cell viability in the presence of shikonin. Elevated ROS levels and mitochondrial dysfunction were also found in shikonin treatment groups. Pretreatment with N-acetyl cysteine remarkably mitigated shikonin-induced cell death and ROS generation. Western blot analysis revealed that shikonin reduced pro-PARP, pro-caspase-3, and Bcl-2 expression and increased cleavage PARP expression. Enhanced autophagy was also found in the shikonin-treated group as evidenced by acridine orange staining. Moreover, light chain 3B (LC3B)-II accumulation and enhanced p62 expression indicated that autophagy occurred in the shikonin-treated group. LC3B knockdown considerably recovered cell viability in the presence of shikonin. Shikonin treatment elevated p38 activity in a dose-dependent manner. In conclusion, our results revealed that shikonin triggered programmed cell death via the elevation of ROS level and p38 activity in different types of RCC cells. These findings suggested that shikonin may be a potential anti-RCC agent.

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Faculty Opinions recommendation of Yeast cell death during DNA damage arrest is independent of caspase or reactive oxygen species.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1020540.232652 ◽

2004 ◽

Author(s):

Mark Rose

Keyword(s):

Reactive Oxygen Species ◽

Dna Damage ◽

Cell Death ◽

Yeast Cell ◽

Reactive Oxygen ◽

Oxygen Species

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CBIO-07. CELL DEATH INDUCED BY AN OSCILLATING MAGNETIC FIELD IN PATIENT DERIVED GLIOBLASTOMA CELLS IS MEDIATED BY REACTIVE OXYGEN SPECIES

Neuro-Oncology ◽

10.1093/neuonc/noaa215.067 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii17-ii17

Author(s):

Shashank Hambarde ◽

Martyn Sharpe ◽

David Baskin ◽

Santosh Helekar

Keyword(s):

Reactive Oxygen Species ◽

Cell Death ◽

Cell Viability ◽

Cortical Neurons ◽

Reactive Oxygen ◽

Great Promise ◽

Antioxidant Vitamin ◽

Ros Generation ◽

Oxygen Species ◽

Novel Therapy

Abstract Noninvasive cancer therapy with minimal side effects would be ideal for improving patient outcome in the clinic. We have developed a novel therapy using strong rotating magnets mounted on a helmet. They generate oscillating magnetic fields (OMF) that penetrate through the skull and cover the entire brain. We have demonstrated that OMF can effectively kill patient derived glioblastoma (GBM) cells in cell culture without having cytotoxic effects on cortical neurons and normal human astrocytes (NHA). Exposure of GBM cells to OMF reduced the cell viability by 33% in comparison to sham-treated cells (p< 0.001), while not affecting NHA cell viability. Time lapse video-microscopy for 16 h after OMF exposure showed a marked elevation of mitochondrial reactive oxygen species (ROS), and rapid apoptosis of GBM cells due to activation of caspase 3. Addition of a potent antioxidant vitamin E analog Trolox effectively blocked OMF-induced GBM cell death. Furthermore, OMF significantly potentiated the cytotoxic effect of the pro-oxidant Benzylamine. The results of our studies demonstrate that OMF-induced cell death is mediated by ROS generation. These results demonstrate a potent oncolytic effect on GBM cells that is novel and unrelated to any previously described therapy, including a very different mechanism of action and different technology compared to Optune therapy. The effect is very powerful, and unlike Optune, can be seen within hours after initiation of treatment. We believe that this technology holds great promise for new, effective and nontoxic treatment of glioblastoma.

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