scholarly journals Dysregulation of Catalase by a Sulphamoylated Estradiol Analogue Culminates in Antimitotic Activity and Cell Death Induction in Breast Cancer Cell Lines

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 622
Author(s):  
Maphuti T. Lebelo ◽  
Anna M. Joubert ◽  
Michelle H. Visagie
Keyword(s):  
Breast Cancer ◽  
Reactive Oxygen Species ◽  
Hydrogen Peroxide ◽  
Cell Death ◽  
Cell Lines ◽  
Superoxide Anion ◽  
Peroxyl Radical ◽  
Breast Cancer Cell Lines ◽  
Oxygen Species ◽  
Antimitotic Activity

Recent findings revealed that 2-ethyl-17-oxoestra-1,3,5(10)-trien-3-yl sulfamate (ESE-one) induces antiproliferative activity and cell rounding dependent on the generation of superoxide anion, hydrogen peroxide and peroxyl radical. In the current study, the role of these reactive oxygen species was assessed in the activity exerted by ESE-one on cell cycle progression, mitochondrial membrane potential and cell death induction in breast tumorigenic cells. The influence of ESE-one was also investigated on superoxide dismutase and catalase activity. ESE-one induced a time-dependent accumulation of cells in the G1 phase and G2/M phase that is partially impaired by tiron and trolox and N,N′-dimethylthiourea suggesting that superoxide anion, hydrogen peroxide and peroxyl radical are required for these effects exerted by ESE-one. Flow cytometry data in MCF-7 cells demonstrated that tiron decreased depolarization of the membrane potential in ESE-one exposed cells, indicating that superoxide anion plays a role in the depolarization effects induced by ESE-one. Spectrophotometry data showed that ESE-one decreased catalase activity in both cell lines. This study contributes towards pertinent information regarding the effects of an in silico-designed sulfamoylated compound on antioxidant enzymes leading to aberrant quantities of specific reactive oxygen species resulting in antimitotic activity culminating in the induction of cell death in breast cancer cell lines.

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.

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

scholarly journals Sulphamoylated Estradiol Analogue Induces Reactive Oxygen Species Generation to Exert Its Antiproliferative Activity in Breast Cancer Cell Lines

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4337
Author(s):  
Maphuti T. Lebelo ◽  
Anna M. Joubert ◽  
Michelle H. Visagie
Keyword(s):  
Reactive Oxygen Species ◽  
Hydrogen Peroxide ◽  
Superoxide Anion ◽  
Fluorescent Microscopy ◽  
Reactive Oxygen ◽  
Breast Cancer Cell Lines ◽  
Oxygen Species ◽  
Morphological Studies ◽  
Mcf 7

2-Methoxyestradiol (2ME), a 17β-estradiol metabolite, exerts anticancer properties in vitro and in vivo. To address 2ME’s low bioavailability, research led to the in silico design of sulphamoylated 2ME analogues. However, the role of oxidative stress induced in the activity exerted by sulphamoylated compounds remains elusive. In the current study, the influence of 2-Ethyl-17-oxoestra-1,3,5(10)-trien-3-yl sulphamate (ESE-one) on reactive oxygen species (ROS) induction and its effect on cell proliferation, as well as morphology, were assessed in breast tumorigenic cells (MCF-7 and MDA-MB-231). Fluorescent microscopy showed that sulphamoylated estradiol analogues induced hydrogen peroxide and superoxide anion, correlating with decreased cell growth demonstrated by spectrophotometry data. ESE-one exposure resulted in antiproliferation which was repressed by tiron (superoxide inhibitor), trolox (peroxyl inhibitor) and N,N′-dimethylthiourea (DMTU) (hydrogen peroxide inhibitor). Morphological studies demonstrated that tiron, trolox and DMTU significantly decreased the number of rounded cells and shrunken cells in MCF-7 and MDA-MB-231 cells induced by ESE-one. This in vitro study suggests that ESE-one induces growth inhibition and cell rounding by production of superoxide anion, peroxyl radical and hydrogen peroxide. Identification of these biological changes in cancer cells caused by sulphamoylated compounds hugely contributes towards improvement of anticancer strategies and the ROS-dependent cell death pathways in tumorigenic breast cells.

scholarly journals Reduction of Intracellular-Reactive Oxygen Species and Diminished Mitogen-Activated Protein Kinases (MAPKs) Activation are Associated with Oral Squamous Cell Carcinoma Cell Aggressiveness

2017 ◽  
Vol 15 (2) ◽  
pp. 131-141
Author(s):  
Tanyarath UTAIPAN ◽  
Apsorn SATTAYAKHOM ◽  
Issara PRACHONGSAI ◽  
Nurdina CHARONG ◽  
Warangkana CHUNGLOK
Keyword(s):  
Reactive Oxygen Species ◽  
Hydrogen Peroxide ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Protein Kinases ◽  
Cell Lines ◽  
Oxygen Species ◽  
Mitogen Activated Protein Kinases ◽  
Mitogen Activated Protein

Oral squamous cell carcinoma (OSCC) is a serious health problem in many countries. Several drugs have been used to treat head and neck and oral cavity cancers. However, the success rate has not been impressive because of the heterogeneity of cancerous cells, resulting in differential responsiveness to chemotherapy. Two distinct phenotypes of OSCC cells, the CLS-354/WT and CLS-354/DXcells, have been used as in vitro cell models for this study. CLS-354/DXcells were more aggressive than CLS-354/WTcells, supported by the observation that CLS-354/DXcells can undergo epithelial-mesenchymal transition (EMT), grow anchorage-independently, and increase invasiveness. We investigated the preliminary redox status of these 2 cell lines, including levels of reactive oxygen species (ROS) and cellular antioxidants, using flow cytometry analysis and ABTS+ free radical scavenging assay, respectively. A 7-fold decrease in ROS level was detected in CLS-354/DXcells, comparing with CLS-354/WTcells, while antioxidant capacity was not different from that of CLS-354/WT cells. Hydrogen peroxide, a ROS modulating agent, could induce ROS levels, and caused cell death in CLS-354/WT greater than that of CLS-354/DX cells. Of note, hydrogen peroxide-induced cytotoxicity could be rescued by N-acetyl cysteine, confirming ROS-mediated cytotoxicity in both cell lines. ROS-sensitive mitogen-activated protein kinases (MAPKs) were observed using immunoblot assay. The expressions of p-JNK1/2 and p-p38 MAPK in CLS-354/DX cells were absent, while these expressions were abundantly detected in CLS-354/WTcells. This suggests that lower ROS levels, with the concomitant reduction of JNK and p38 MAPK activation in CLS-354/DX cells, are associated with cancer cell aggressiveness. These findings provide significant evidence of the resistance to ROS-modulating agents in aggressive OSCC cells.

scholarly journals Peptide-Templated Gold Clusters as Enzyme-Like Catalyst Boost Intracellular Oxidative Pressure and Induce Tumor-Specific Cell Apoptosis

Nanomaterials ◽  
2018 ◽  
Vol 8 (12) ◽  
pp. 1040 ◽  
Author(s):  
Ya Zhang ◽  
Xiangchun Zhang ◽  
Qing Yuan ◽  
Wenchao Niu ◽  
Chunyu Zhang ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Hydrogen Peroxide ◽  
Cell Apoptosis ◽  
Superoxide Anion ◽  
Reactive Oxygen ◽  
Gold Clusters ◽  
Specific Cell ◽  
Oxygen Species ◽  
Potential Damage

Anticancer metallodrugs that aim to physiological characters unique to tumor microenvironment are expected to combat drug tolerance and side-effects. Recently, owing to the fact that reactive oxygen species’ is closely related to the development of tumors, people are committed to developing metallodrugs with the capacity of improving the level of reactive oxygen species level toinduce oxidative stress in cancer cells. Herein, we demonstrated that peptide templated gold clusters with atomic precision preferably catalyze the transformation of hydrogen peroxide into superoxide anion in oxidative pressure-type tumor cells. Firstly, we successfully constructed gold clusters by rationally designing peptide sequences which targets integrin ανβ3 overexpressed on glioblastoma cells. The superoxide anion, radical derived from hydrogen peroxide and catalyzed by gold clusters, was confirmed in vitro under pseudo-physiological conditions. Then, kinetic parameters were evaluated to verify the catalytic properties of gold clusters. Furthermore, these peptide decorated clusters can serve as special enzyme-like catalyst to convert endogenous hydrogen peroxide into superoxide anion, elevated intracellular reactive oxygen species levels, lower mitochondrial membrane potential, damage biomacromolecules, and trigger tumor cell apoptosis consequently.

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