Induction of Apoptosis in Human Multiple Myeloma Cell Lines by Ebselen via Enhancing the Endogenous Reactive Oxygen Species Production

Zhang, Liang; Zhou, Li-Wei; Du, Jie; Li, Mengxia; Qian, Chengyuan; Cheng, Yi; Yang, Peng; Xie, Jing; Wang, Dong

doi:10.1155/2014/696107

Cited by 26 publications

(30 citation statements)

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“…Although toxic effects of this drug were unexpected, because the selenium in ebselen is not released, is not bioavailable and ebselen metabolites are excreted in bile and urine, 29 experimental evidence shows that ebselen causes cell death in several cancer cell types, including AR42J cells. 8,9 The concentrations of ebselen that we have employed fall within the range of concentrations employed by others, which vary between 1 and 40 μM, and have reported protective effects of the compound. 30,31 However, previous studies carried out in our laboratory have shown that ebselen may cause damage to the cells.…”

Section: Effect Of Ebselen On Mitogen-activated Protein Kinasesmentioning

confidence: 86%

“…6 However, deleterious effects of ebselen have been also reported. Ebselen sensitizes glioma cells to TNFalphainduced apoptosis, 7 induces cell death in AR42J cells, 8 induces apoptosis in human multiple myeloma cell lines, 9 increases the toxicity of copper in astrocytes, 10 and inhibits hepatitis C virus NS3 helicase binding to nucleic acid and prevents viral replication. 11 Moreover, anti-neoplastic properties of ebselen in pancreatic and renal cancer cell lines have been reported.…”

Section: Introductionmentioning

confidence: 99%

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Ebselen impairs cellular oxidative state and induces endoplasmic reticulum stress and activation of crucial mitogen‐activated protein kinases in pancreatic tumour AR42J cells

Santofimia‐Castaño

Izquierdo-Álvarez

Plaza-Dávila

et al. 2017

J of Cellular Biochemistry

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Ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one) is an organoselenium radical scavenger compound, which has strong antioxidant and anti-inflammatory effects. However, evidence suggests that this compound could exert deleterious actions on cell physiology. In this study, we have analyzed the effect of ebselen on rat pancreatic AR42J cells. Cytosolic free-Ca concentration ([Ca ] ), cellular oxidative status, setting of endoplasmic reticulum stress, and phosphorylation of major mitogen-activated protein kinases were analyzed. Our results show that ebselen evoked a concentration-dependent increase in [Ca ] . The compound induced an increase in the generation of reactive oxygen species in the mitochondria. We also observed an increase in global cysteine oxidation in the presence of ebselen. In the presence of ebselen an impairment of cholecystokinin-evoked amylase release was noted. Moreover, involvement of the unfolded protein response markers, ER chaperone and signaling regulator GRP78/BiP, eukaryotic translation initiation factor 2α and X-box binding protein 1 was detected. Finally, increases in the phosphorylation of SAPK/JNK, p38 MAPK, and p44/42 MAPK in the presence of ebselen were also observed. Our results provide evidences for an impairment of cellular oxidative state and enzyme secretion, the induction of endoplasmic reticulum stress and the activation of crucial mitogen-activated protein kinases in the presence of ebselen. As a consequence ebselen exerts a potential toxic effect on AR42J cells.

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Section: Effect Of Ebselen On Mitogen-activated Protein Kinasesmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Ebselen impairs cellular oxidative state and induces endoplasmic reticulum stress and activation of crucial mitogen‐activated protein kinases in pancreatic tumour AR42J cells

Santofimia‐Castaño

Izquierdo-Álvarez

Plaza-Dávila

et al. 2017

J of Cellular Biochemistry

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“…Free radicals such as ROS and NO are known to induce oxidative stress, subsequently impairing mitochondrial function [21]. Recent studies have demonstrated that the production of ROS increases, as followed by Bax translocation, and then triggers the cell apoptosis [22]. A strong…”

Section: Lps Accelerates Srm 2786-induced Cell Apoptosis In 16hbe Cellsmentioning

confidence: 99%

Lipopolysaccharide accelerates fine particulate matter-induced cell apoptosis in human lung bronchial epithelial cells

Xiong

Chen

et al. 2017

Int J Occup Med Environ Health

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Objectives: The aim of the study has been to investigate the effect of the Standard Reference Material of fine particulate matter (SRM 2786) on cytotoxicity and apoptosis in human lung bronchial epithelial cells (16HBE cells). Whether the lipopolysaccharide (LPS)-induced inflammation could further accelerate cell apoptosis induced by SRM 2786 stimulation has also been determined. Material and Methods: 16HBE cells were exposed to various doses of SRM 2786 with or without LPS. The following parameters: cytotoxicity, apoptotic rate, Bax/Bcl-2 expression, nitric oxide (NO) production, and reactive oxygen species (ROS) generation were measured. Results: The results have shown that SRM 2786 induces cell damage and apoptosis of 16HBE cells as demonstrated by significant decrease in expression of Bcl-2 and increase in expression of Bax. When compared with the control cells, the apoptotic rate of cells treated by 500 μg/ml of SRM 2786 increased from 2.43±0.21% to 43.96±2.95% (p < 0.01). Further, there was an elevated production of NO and ROS post SRM 2786 treatment. The level of NO in cells treated with 500 μg/ml of SRM 2786 was 18.33±1.02 μmol/l whereas that of control cells was 1.58±0.31 μmol/l (p < 0.01). When compared with the control group, the level of intracellular ROS increased by 24% after treatment with 500 μg/ml of SRM 2786 (p < 0.05). In addition, LPS pre-treatment may accelerate cell apoptosis by increasing generation of NO and ROS followed by SRM 2786 stimulation. When compared to cells treated with 125 μg/ml of SRM 2786 alone, the levels of NO and ROS in cells pretreated with LPS increased by 28% and 11.6%, respectively (p < 0.05), and the apoptotic rate increased from 34.62±4.44% to 54.11±3.34% (p < 0.01). Conclusions: These findings have suggested that in vitro exposure to SRM 2786 could induce 16HBE cells apoptosis probably by means of the mechanism involving the generation of free radicals, while the degree of apoptosis would be further aggravated under inflammation condition. Int J Occup Med Environ Health 2018;31(2):173 -183

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“…Then it causes the release of cytochrome c. Cytochrome c is released into the cytosol and activates a family of caspases. Then a series of cascade reactions are triggered [17][18][19]. Studies have shown that the increased production of reactive oxygen species (ROS) also induces a decrease in the mitochondrial membrane potential, followed by the release of cytochrome c, which ultimately leads to apoptosis [20,21].…”

Section: Introductionmentioning

confidence: 99%

Novel Anthraquinone Compounds Inhibit Colon Cancer Cell Proliferation via the Reactive Oxygen Species/JNK Pathway

Guo

Guan

et al. 2020

Molecules

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A series of amide anthraquinone derivatives, an important component of some traditional Chinese medicines, were structurally modified and the resulting antitumor activities were evaluated. The compounds showed potent anti-proliferative activities against eight human cancer cell lines, with no noticeable cytotoxicity towards normal cells. Among the candidate compounds, 1-nitro-2-acyl anthraquinone-leucine (8a) showed the greatest inhibition of HCT116 cell activity with an IC50 of 17.80 μg/mL. In addition, a correlation model was established in a three-dimensional quantitative structure-activity relationship (3D-QSAR) study using Comparative Molecular Field Analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA). Moreover, compound 8a effectively killed tumor cells by reactive oxygen species (ROS)-JNK activation, causing an increase in ROS levels, JNK phosphorylation, and mitochondrial stress. Cytochrome c was then released into cytoplasm, which, in turn activated the cysteine protease pathway and ultimately induced tumor cell apoptosis, suggesting a potential use of this compound for colon cancer treatment.

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Induction of Apoptosis in Human Multiple Myeloma Cell Lines by Ebselen via Enhancing the Endogenous Reactive Oxygen Species Production

Cited by 26 publications

References 50 publications

Ebselen impairs cellular oxidative state and induces endoplasmic reticulum stress and activation of crucial mitogen‐activated protein kinases in pancreatic tumour AR42J cells

Ebselen impairs cellular oxidative state and induces endoplasmic reticulum stress and activation of crucial mitogen‐activated protein kinases in pancreatic tumour AR42J cells

Lipopolysaccharide accelerates fine particulate matter-induced cell apoptosis in human lung bronchial epithelial cells

Novel Anthraquinone Compounds Inhibit Colon Cancer Cell Proliferation via the Reactive Oxygen Species/JNK Pathway

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