scholarly journals Towards an Understanding of Specific Response of Metallothionein (Sub)Isoforms to Exposure to Platinum-Based Anticancer Drugs

2019 ◽  
Vol 67 (6) ◽  
pp. 1407-1417
Author(s):  
Sofie Blížkovská
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Free Radicals ◽  
Fluorescence Microscopy ◽  
Cancer Cells ◽  
Protein Level ◽  
Poor Prognosis ◽  
Cell Stress ◽  
Specific Response ◽  
Oxygen Species

Metallothioneins (MTs) are small cysteine-rich proteins involved in a number of pathophysiological processes. Particularly their linkage to cancer processes has been vastly studied and it is well known that MTs can inactivate metal-based cytostatics or scavenge free radicals. These processes result in pronounced chemoresistance and a poor prognosis for patients. Despite this knowledge, involvement of specific (sub)isoforms into this phenomenon requires further elucidation. Our results identified CisPt as the cytostatic which provoked the highest cell death exp followed by CarboPt and OxaliPt. Fluorescence microscopy visualized the oxidative cell stress. After application of 24hIC50 values, the reactive oxygen species (ROS) were visually produced. Our results also showed that MT 1, 2 and 3 expression manifested the highest qPCR activity after CisPt treatment (both healthy and cancer cells). While evaluating the expression of the protein level in the healthy and cancer cells treated by the cytotoxics we concluded that for MT1 and MT3 it was low under all three cytostatic treatments. Cancer cells had higher protein expression levels than healthy cells. In case of MT1/2 for cancer cells was highest under CisPt treatment.

scholarly journals AKT but not MYC promotes reactive oxygen species-mediated cell death in oxidative culture

2019 ◽  
Author(s):  
Dongqing Zheng ◽  
Jonathan H. Sussman ◽  
Matthew P. Jeon ◽  
Sydney T. Parrish ◽  
Alireza Delfarah ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Reactive Oxygen Species ◽  
Cell Death ◽  
Oxidative Phosphorylation ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cell Lines ◽  
Oxygen Species

ABSTRACTOncogenes can generate metabolic vulnerabilities in cancer cells. Here, we tested how AKT and MYC affect the ability of cells to shift between respiration and glycolysis. Using immortalized mammary epithelial cells, we discovered that constitutively active AKT but not MYC induced cell death in galactose culture, where cells must rely on oxidative phosphorylation for energy generation. However, the negative effects of AKT were short-lived, and AKT-expressing cells recommenced growth after ~15 days in galactose. To identify the mechanisms regulating AKT-mediated cell death, we used metabolomics and found that AKT cells dying in galactose upregulated glutathione metabolism. Next, using proteomics, we discovered that AKT-expressing cells dying in galactose upregulated nonsense-mediated mRNA decay, a marker of sensitivity to oxidative stress. We therefore measured levels of reactive oxygen species (ROS) and discovered that galactose induced ROS in cells expressing AKT but not MYC. Additionally, ROS were required for the galactose-induced death of AKT-expressing cells. We then tested whether these findings could be replicated in breast cancer cell lines with constitutively active AKT signaling. Indeed, we found that galactose induced rapid cell death in breast cancer cell lines and that ROS were required for galactose-induced cell death. Together, our results demonstrate that AKT but not MYC induces a metabolic vulnerability in cancer cells, namely the restricted flexibility to use oxidative phosphorylation.ImplicationsThe discovery that AKT but not MYC restricts the ability to utilize oxidative phosphorylation highlights that therapeutics targeting tumor metabolism must be tailored to the individual genetic profile of tumors.

MG132 as a proteasome inhibitor induces cell growth inhibition and cell death in A549 lung cancer cells via influencing reactive oxygen species and GSH level

2010 ◽  
Vol 29 (7) ◽  
pp. 607-614 ◽  
Author(s):  
Yong Hwan Han ◽  
Woo Hyun Park
Keyword(s):  
Lung Cancer ◽  
Reactive Oxygen Species ◽  
Cell Cycle ◽  
Cell Death ◽  
Cancer Cells ◽  
Proteasome Inhibitor ◽  
A549 Cells ◽  
Lung Cancer Cells ◽  
Oxygen Species ◽  
A549 Lung

Carbobenzoxy-Leu-Leu-leucinal (MG132) as a proteasome inhibitor has been shown to induce apoptotic cell death through formation of reactive oxygen species (ROS). In the present study, we evaluated the effects of MG132 on the growth of A549 lung cancer cells in relation to cell growth, ROS and glutathione (GSH) levels. Treatment with MG132 inhibited the growth of A549 cells with an IC50 of approximately 20 μM at 24 hours. DNA flow cytometric analysis indicated that 0.5 ∼ 30 μM MG132 induced a G1 phase arrest of the cell cycle in A549 cells. Treatment with 10 or 30 μM MG132 also induced apoptosis, as evidenced by sub-G1 cells and annexin V staining cells. This was accompanied by the loss of mitochondrial membrane potential (MMP; Δψm). The intracellular ROS levels including O2•- were strongly increased in 10 or 30 μM MG132-treated A549 cells but were down-regulated in 0.1, 0.5 or 1 μM MG132-treated cells. Furthermore, 10 or 30 μM MG132 increased mitochondrial O2•- level but 0.1, 0.5 or 1 μM MG132 decreased that. In addition, 10 or 30 μM MG132 induced GSH depletion in A549 cells. In conclusion, MG132 inhibited the growth of human A549 cells via inducing the cell cycle arrest as well as triggering apoptosis, which was in part correlated with the changes of ROS and GSH levels. Our present data provide important information on the anti-growth mechanisms of MG132 in A549 lung cancer cells in relation to ROS and GSH.

Mitochondrion-targeted selenium nanoparticles enhance reactive oxygen species-mediated cell death

Nanoscale ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 1389-1396 ◽  
Author(s):  
Yuan Zhuang ◽  
Longjie Li ◽  
Liandong Feng ◽  
Shuangshuang Wang ◽  
Huimin Su ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Cancer Cells ◽  
Reactive Oxygen ◽  
Selenium Nanoparticles ◽  
Oxygen Species ◽  
Targeting Ability ◽  
Mitochondria Targeting

Selenium nanoparticles (SeNPs) with mitochondria targeting ability can significantly enhance the reactive oxygen species (ROS) induced cell death in cancer cells, while remaining less toxic in healthy cells.

scholarly journals Molecular interaction and cellular studies on combination photodynamic therapy with rutoside for melanoma A375 cancer cells: an in vitro study

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Khatereh Khorsandi ◽  
Reza Hosseinzadeh ◽  
Elham Chamani
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Cycle ◽  
Cell Death ◽  
Photodynamic Therapy ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Human Melanoma ◽  
Oxygen Species ◽  
Melanoma Cancer

Abstract Background Melanoma as a type of skin cancer, is associated with a high mortality rate. Therefore, early diagnosis and efficient surgical treatment of this disease is very important. Photodynamic therapy (PDT) involves the activation of a photosensitizer by light at specific wavelength that interacts with oxygen and creates singlet oxygen molecules or reactive oxygen species (ROS), which can lead to tumor cell death. Furthermore, one of the main approches in the prevention and treatment of various cancers is plant compounds application. Phenolic compounds are essential class of natural antioxidants, which play crucial biological roles such as anticancer effects. It was previously suggested that flavonoid such as rutoside could acts as pro-oxidant or antioxidant. Hence, in this study, we aimed to investigate the effect of rutoside on the combination therapy with methylene blue (MB) assisted by photodynamic treatment (PDT) using red light source (660 nm; power density: 30 mW/cm2) on A375 human melanoma cancer cells. Methods For this purpose, the A375 human melanoma cancer cell lines were treated by MB-PDT and rutoside. Clonogenic cell survival, MTT assay, and cell death mechanisms were also determined after performing the treatment. Subsequently, after the rutoside treatment and photodynamic therapy (PDT), cell cycle and intracellular reactive oxygen species (ROS) generation were measured. Results The obtained results showed that, MB-PDT and rutoside had better cytotoxic and antiprolifrative effects on A375 melanoma cancer cells compared to each free drug, whereas the cytotoxic effect on HDF human dermal fibroblast cell was not significant. MB-PDT and rutoside combination induced apoptosis and cell cycle arrest in the human melanoma cancer cell line. Intracellular ROS increased in A375 cancer cell line after the treatment with MB-PDT and rutoside. Conclusion The results suggest that, MB-PDT and rutoside could be considered as novel approaches as the combination treatment of melanoma cancer.

JLP-JNK signaling protects cancer cells from reactive oxygen species-induced cell death

2018 ◽  
Vol 501 (3) ◽  
pp. 724-730 ◽  
Author(s):  
Rong Li ◽  
I. Ketut Gunarta ◽  
Ryusuke Suzuki ◽  
Jambaldorj Boldbaatar ◽  
Ryota Nakazato ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Cancer Cells ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Jnk Signaling

An Isoquinolin-1(2H )-Imine Derivative Induces Cell Death via Generation of Reactive Oxygen Species and Activation of JNK in Human A549 Cancer Cells

2017 ◽  
Vol 118 (12) ◽  
pp. 4394-4403
Author(s):  
Jing Liu ◽  
Tongyang Liu ◽  
Hanchuan Mou ◽  
Shuting Jia ◽  
Chao Huang ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Cancer Cells ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Human A549
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