scholarly journals Dihydroceramide accumulation and reactive oxygen species are distinct and nonessential events in 4-HPR-mediated leukemia cell death

2012 ◽  
Vol 90 (2) ◽  
pp. 209-223 ◽  
Author(s):  
Aintzane Apraiz ◽  
Jolanta Idkowiak-Baldys ◽  
Naiara Nieto-Rementería ◽  
María Dolores Boyano ◽  
Yusuf A Hannun ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Vitamin E ◽  
Leukemia Cell ◽  
Reactive Oxygen ◽  
Jurkat Cells ◽  
Human Leukemia ◽  
Ros Production ◽  
Oxygen Species ◽  
Independent Events

4-(Hydroxyphenyl)retinamide (4-HPR) is a synthetic retinoid with a strong apoptotic effect towards different cancer cell lines in vitro, and it is currently tested in clinical trials. Increases of reactive oxygen species (ROS) and modulation of endogenous sphingolipid levels are well-described events observed upon 4-HPR treatment, but there is still a lack of understanding of their relationship and their contribution to cell death. LC–MS analysis of sphingolipids revealed that in human leukemia CCRF-CEM and Jurkat cells, 4-HPR induced dihydroceramide but not ceramide accumulation even at sublethal concentrations. Myriocin prevented the 4-HPR-induced dihydroceramide accumulation, but it did not prevent the loss of viability and increase of intracellular ROS production. On the other hand, ascorbic acid, Trolox, and vitamin E reversed 4-HPR effects on cell death but not dihydroceramide accumulation. NDGA, described as a lipoxygenase inhibitor, exerted a significantly higher antioxidant activity than vitamin E and abrogated 4-HPR-mediated ROS. It did not however rescue cellular viability. Taken together, this study demonstrates that early changes observed upon 4-HPR treatment, i.e., sphingolipid modulation and ROS production, are mechanistically independent events. Furthermore, the results indicate that 4-HPR-driven cell death may occur even in the absence of dihydroceramide or ROS accumulation. These observations should be taken into account for an improved design of drug combinations.

N-(4-Hydroxyphenyl)retinamide (4-HPR) Induces Leukemia Cell Death via Generation of Reactive Oxygen Species

2003 ◽  
Vol 78 (3) ◽  
pp. 219-225 ◽  
Author(s):  
Hiroaki Goto ◽  
Hiroyuki Takahashi ◽  
Hisaki Fujii ◽  
Koichiro Ikuta ◽  
Shumpei Yokota
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Leukemia Cell ◽  
Reactive Oxygen ◽  
Oxygen Species

scholarly journals The Characterization of TA-289, a Novel Antifungal from Fusarium sp.

2021 ◽  
Author(s):  
◽  
Natelle C H Quek
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Cell Cycle ◽  
Cell Death ◽  
Reactive Oxygen ◽  
Chemical Diversity ◽  
Mitochondrial Morphology ◽  
Ros Production ◽  
Oxygen Species ◽  
Wild Type

<p>Natural products offer vast structural and chemical diversity highly sought after in drug discovery research. Saccharomyces cerevisiae makes an ideal model eukaryotic organism for drug mode-of-action studies owing to ease of growth, sophistication of genetic tools and overall homology to higher eukaryotes. Equisetin and a closely related novel natural product, TA-289, are cytotoxic to fermenting yeast, but seemingly less so when yeast actively respire. Cell cycle analyses by flow cytometry revealed a cell cycle block at S-G2/M phase caused by TA-289; previously described oxidative stress-inducing compounds causing cell cycle delay led to further investigation in the involvement of equisetin and TA-289 in mitochondrial-mediated generation of reactive oxygen species. Chemical genomic profiling involving genome-wide scans of yeast deletion mutant strains for TA-289 sensitivity revealed sensitization of genes involved in the mitochondria, DNA damage repair and oxidative stress responses, consistent with a possible mechanism-of-action at the mitochondrion. Flow cytometric detection of reactive oxygen species (ROS) generation caused by TA-289 suggests that the compound may induce cell death via ROS production. The generation of a mutant strain resistant to TA-289 also displayed resistance to a known oxidant, H2O2, at concentrations that were cytotoxic to wild-type cells. The resistant mutant displayed a higher basal level of ROS production compared to the wild-type parent, indicating that the resistance mutation led to an up-regulation of antioxidant capacity which provides cell survival in the presence of TA-289. Yeast mitochondrial morphology was visualized by confocal light microscopy, where it was observed that cells treated with TA-289 displayed abnormal mitochondria phenotypes, further indicating that the compound is acting primarily at the mitochondrion. Similar effects observed with equisetin treatment suggest that both compounds share the same mechanism, eliciting cell death via ROS production in the mitochondrial respiratory chain.</p>

scholarly journals Survival Signaling by C-RAF: Mitochondrial Reactive Oxygen Species and Ca2+ Are Critical Targets

2008 ◽  
Vol 28 (7) ◽  
pp. 2304-2313 ◽  
Author(s):  
Andrey V. Kuznetsov ◽  
Julija Smigelskaite ◽  
Christine Doblander ◽  
Manickam Janakiraman ◽  
Martin Hermann ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Cell Death ◽  
Reactive Oxygen ◽  
Ros Production ◽  
Oxygen Species ◽  
Mitochondrial Reactive Oxygen Species ◽  
Mitochondrial Ros ◽  
Survival Signaling ◽  
First Time

ABSTRACT Survival signaling by RAF occurs through largely unknown mechanisms. Here we provide evidence for the first time that RAF controls cell survival by maintaining permissive levels of mitochondrial reactive oxygen species (ROS) and Ca2+. Interleukin-3 (IL-3) withdrawal from 32D cells resulted in ROS production, which was suppressed by activated C-RAF. Oncogenic C-RAF decreased the percentage of apoptotic cells following treatment with staurosporine or the oxidative stress-inducing agent tert-butyl hydroperoxide. However, it was also the case that in parental 32D cells growing in the presence of IL-3, inhibition of RAF signaling resulted in elevated mitochondrial ROS and Ca2+ levels. Cell death is preceded by a ROS-dependent increase in mitochondrial Ca2+, which was absent from cells expressing transforming C-RAF. Prevention of mitochondrial Ca2+ overload after IL-3 deprivation increased cell viability. MEK was essential for the mitochondrial effects of RAF. In summary, our data show that survival control by C-RAF involves controlling ROS production, which otherwise perturbs mitochondrial Ca2+ homeostasis.

Caspase-independent cell death without generation of reactive oxygen species in irradiated MOLT-4 human leukemia cells

2009 ◽  
Vol 255 (1-2) ◽  
pp. 61-68 ◽  
Author(s):  
Kengo Yoshida ◽  
Yoshiko Kubo ◽  
Yoichiro Kusunoki ◽  
Yukari Morishita ◽  
Hiroko Nagamura ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Reactive Oxygen ◽  
Leukemia Cells ◽  
Human Leukemia ◽  
Oxygen Species ◽  
Human Leukemia Cells

scholarly journals Bufalin Induces Reactive Oxygen Species Dependent Bax Translocation and Apoptosis in ASTC-a-1 Cells

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Lei Sun ◽  
Tongsheng Chen ◽  
Xiaoping Wang ◽  
Yun Chen ◽  
Xunbin Wei
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Temporal Dynamics ◽  
Reactive Oxygen ◽  
Ros Generation ◽  
Ros Production ◽  
Oxygen Species ◽  
Induced Apoptosis

Bufalin has been shown to induce cancer cell death through apoptotic pathways. However, the molecular mechanisms are not well understood. In this study, we used the confocal fluorescence microscopy (CFM) to monitor the spatio-temporal dynamics of reactive oxygen species (ROS) production, Bax translocation and caspase-3 activation during bufalin-induced apoptosis in living human lung adenocarcinoma (ASTC-a-1) cells. Bufalin induced ROS production and apoptotic cell death, demonstrated by Hoechst 33258 staining as well as flow cytometry analysis. Bax redistributed from cytosol to mitochondria from 12 to 48 h after bufalin treatment in living cells expressed with green fluorescent protein Bax. Treatment with the antioxidantN-acetyl-cysteine (NAC), a ROS scavenger, inhibited ROS generation and Bax translocation and led to a significant protection against bufalin-induced apoptosis. Our results also revealed that bufalin induced a prominent increase of caspase-3 activation blocked potently by NAC. Taken together, bufalin induced ROS-mediated Bax translocation, mitochondrial permeability transition and caspase-3 activation, implying that bufalin induced apoptosis via ROS-dependent mitochondrial death pathway in ASTC-a-1 cells.

(6)-Gingerolinduced myeloid leukemia cell death is initiated by reactive oxygen species and activation of miR-27b expression

2014 ◽  
Vol 68 ◽  
pp. 288-301 ◽  
Author(s):  
Namrata Rastogi ◽  
Rishi Kumar Gara ◽  
Rachana Trivedi ◽  
Akanksha Singh ◽  
Preety Dixit ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Myeloid Leukemia ◽  
Leukemia Cell ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Myeloid Leukemia Cell

scholarly journals Transient Increase in Cellular Dehydrogenase Activity After Cadmium Treatment Precedes Enhanced Production of Reactive Oxygen Species in Human Proximal Tubular Kidney Cells

2019 ◽  
pp. 481-490 ◽  
Author(s):  
J. HANDL ◽  
J. ČAPEK ◽  
P. MAJTNEROVÁ ◽  
F. PETIRA ◽  
M. HAUSCHKE ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Dehydrogenase Activity ◽  
Reactive Oxygen ◽  
Transient Increase ◽  
Kidney Cells ◽  
Ros Production ◽  
Oxygen Species ◽  
Cadmium Treatment ◽  
Jnk Activation

Cadmium is a heavy metal causing toxicity especially in kidney cells. The toxicity is linked also with enhanced oxidative stress leading to cell death. On the other hand, our recent experiments have shown that an increase of total intracellular dehydrogenases activity can also occur in kidney cells before declining until cell death. The aim of the present study, therefore, was to evaluate this transient enhancement in cell viability after cadmium treatment. The human kidney HK-2 cell line was treated with CdCl2 at concentrations 0-200 µM for 2-24 h and intracellular dehydrogenase activity was tested. In addition, we measured reactive oxygen species (ROS) production, glutathione levels, mitochondrial membrane potential, and C-Jun-N-terminal kinase (JNK) activation. We found that significantly increased dehydrogenase activity could occur in cells treated with 25, 100, and 200 µM CdCl2. Moreover, the results showed an increase in ROS production linked with JNK activation following the enhancement of dehydrogenase activity. Other tests detected no relationship with the increased in intracellular dehydrogenase activity. Hence, the transient increase in dehydrogenase activity in HK-2 cells preceded the enhancement of ROS production and our finding provides new evidence in cadmium kidney toxicity.

scholarly journals Effect of ClAlPcS2 photodynamic and sonodynamic therapy on hela cells

2019 ◽  
pp. S375-S384 ◽  
Author(s):  
S. Binder ◽  
B Hosikova ◽  
Z. Mala ◽  
L. Zarska ◽  
H. Kolarova
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Hela Cells ◽  
Cell Damage ◽  
Combined Therapy ◽  
Reactive Oxygen ◽  
Ros Production ◽  
Oxygen Species ◽  
Sonodynamic Therapy ◽  
A Cell

Photodynamic therapy (PDT) uses photosensitive substance to provoke a cytotoxic reaction causing a cell damage or cell death. The substances, photosensitizers, are usually derivates of porphyrine or phtalocyanine. Photosensitizers must be activated by light in order to produce reactive oxygen species, mainly singlet oxygen. Sonodynamic therapy (SDT) utilizes ultrasound to enhance a cytotoxic effects of compounds called sonosensitizers. In this study we investigated photodynamic and sonodynamic effect of chloraluminium phtalocyanine disulfonate (ClAlPcS(2)) on HeLa cells. DNA damage, cell viability and reactive oxygen species (ROS) production were assessed to find whether the combination of PDT and SDT inflicts HeLa cells more than PDT alone. We found that the combined therapy increases DNA fragmentation, enhances ROS production and decreases cell survival. Our results indicate that ClAlPcS(2) can act as a sonosentitiser and combined with PDT causes more irreversible changes to the cells resulting in cell death than PDT alone.

scholarly journals Antioxidants Threaten Multikinase Inhibitor Efficacy against Liver Cancer by Blocking Mitochondrial Reactive Oxygen Species

Antioxidants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1336
Author(s):  
Blanca Cucarull ◽  
Anna Tutusaus ◽  
Tania Hernáez-Alsina ◽  
Pablo García de Frutos ◽  
María Reig ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Liver Cancer ◽  
Cell Lines ◽  
Reactive Oxygen ◽  
Chemotherapeutic Agents ◽  
Glutathione Depletion ◽  
Ros Production ◽  
Oxygen Species ◽  
Tumor Spheroids

Sorafenib and regorafenib, multikinase inhibitors (MKIs) used as standard chemotherapeutic agents for hepatocellular carcinoma (HCC), generate reactive oxygen species (ROS) during cancer treatment. Antioxidant supplements are becoming popular additions to our diet, particularly glutathione derivatives and mitochondrial-directed compounds. To address their possible interference during HCC chemotherapy, we analyzed the effect of common antioxidants using hepatoma cell lines and tumor spheroids. In liver cancer cell lines, sorafenib and regorafenib induced mitochondrial ROS production and potent cell death after glutathione depletion. In contrast, cabozantinib only exhibited oxidative cell death in specific HCC cell lines. After sorafenib and regorafenib administration, antioxidants such as glutathione methyl ester and the superoxide scavenger MnTBAP decreased cell death and ROS production, precluding the MKI activity against hepatoma cells. Interestingly, sorafenib-induced mitochondrial damage caused PINK/Parkin-dependent mitophagy stimulation, altered by increased ROS production. Finally, in sorafenib-treated tumor spheroids, while ROS induction reduced tumor growth, antioxidant treatments favored tumor development. In conclusion, the anti-tumor activity of specific MKIs, such as regorafenib and sorafenib, is altered by the cellular redox status, suggesting that uncontrolled antioxidant intake during HCC treatment should be avoided or only endorsed to diminish chemotherapy-induced side effects, always under medical scrutiny.

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