ROS-mediated endoplasmic reticulum stress and mitochondrial dysfunction underlie apoptosis induced by resveratrol and arsenic trioxide in A549 cells

Gu, Shiyan; Chen, Chengzhi; Jiang, Xuejun; Zhang, Zunzhen

doi:10.1016/j.cbi.2016.01.005

Cited by 103 publications

(57 citation statements)

References 40 publications

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“…In addition, oxidative stress induced by the drugs may be responsible for cell death [12,37] . To verify whether ER stress and/or oxidative stress are associated with Res-006-mediated HepG2 cell death, the ER stress regulator 4-phenylbutyrate (PBA) and/or the ROS inhibitor N-acetyl-Lcysteine (NAC) were applied along with Res-006.…”

Section: Resultsmentioning

confidence: 99%

“…It is possible that mitochondrial dysfunction can induce ER stress [37,39] and vice versa [24,40,41] . To explore this, we first used mitochondria-targeted enhanced yellow fluorescent protein (Mito-EYFP) to monitor the morphological changes of mitochondria during Res-006 treatment in HepG2 cells ( Figure 3A).…”

Section: Res-006 Dysregulates Mitochondrial Dynamics and Disrupts Mmpmentioning

confidence: 99%

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The novel resveratrol derivative 3,5-diethoxy-3′,4′-dihydroxy-trans-stilbene induces mitochondrial ROS-mediated ER stress and cell death in human hepatoma cells in vitro

et al. 2017

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Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a well-known polyphenol that is present in grapes, peanuts, pine seeds, and several other plants. Resveratrol exerts deleterious effects on various types of human cancer cells. Here, we analyzed the cell death-inducing mechanisms of resveratrol-006 (Res-006), a novel resveratrol derivative in human liver cancer cells in vitro. Res-006 suppressed the viability of HepG2 human hepatoma cells more effectively than resveratrol (the IC 50 values were 67.2 and 354.8 μmol/L, respectively). Co-treatment with the ER stress regulator 4-phenylbutyrate (0.5 mmol/L) or the ROS inhibitor N-acetyl-L-cysteine (NAC, 1 mmol/L) significantly attenuated Res-006-induced HepG2 cell death, suggesting that pro-apoptotic ER stress and/or ROS may govern the Res-006-induced HepG2 cell death. We further revealed that treatment of HepG2 cells with Res-006 (65 μmol/L) immediately elicited the dysregulation of mitochondrial dynamics and the accumulation of mitochondrial ROS. It also collapsed the mitochondrial membrane potential and further induced ER stress and cell death. These events, except for the change in mitochondrial morphology, were prevented by the exposure of the HepG2 cells to the mitochondrial ROS scavenger, Mito-TEMPO (300-1000 μmol/L). The results suggest that Res-006 may kill HepG2 cells through cell death pathways, including the ER stress initiated by mitochondrial ROS accumulation. The cell death induced by this novel resveratrol derivative involves crosstalk between the mitochondria and ER stress mechanisms.

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Section: Resultsmentioning

confidence: 99%

Section: Res-006 Dysregulates Mitochondrial Dynamics and Disrupts Mmpmentioning

confidence: 99%

The novel resveratrol derivative 3,5-diethoxy-3′,4′-dihydroxy-trans-stilbene induces mitochondrial ROS-mediated ER stress and cell death in human hepatoma cells in vitro

et al. 2017

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“…Arsenic-induced ROS couples with nitric oxide (NO) producing peroxynitrite (Bunderson et al 2002) and decreases the bioavailability of NO to vascular endothelium and smooth muscle, which likely contributes to cardiovascular complications. ROS have also been shown to result in cell damage and cell death in numerous cell lines and models of arsenic-induced disease pathology (Li et al 2010, Shi et al 2010, Gu et al 2016, Aposhian et al 2003, Abhyankar et al 2012). …”

Section: Introductionmentioning

confidence: 99%

Monomethylarsonous acid, but not inorganic arsenic, is a mitochondria-specific toxicant in vascular smooth muscle cells

Pace

Banerjee

Welch

et al. 2016

Toxicology in Vitro

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Arsenic exposure has been implicated as a risk factor for cardiovascular diseases, metabolic disorders, and cancer, yet the role mitochondrial dysfunction plays in the cellular mechanisms of pathology is largely unknown. To investigate arsenic-induced mitochondrial dysfunction in vascular smooth muscle cells (VSMCs), we exposed rat aortic smooth muscle cells (A7r5) to inorganic arsenic (iAs(III)) and its metabolite monomethylarsonous acid (MMA(III)) and compared their effects on mitochondrial function and oxidative stress. Our results indicate that MMA(III) is significantly more toxic to mitochondria than iAs(III). Exposure of VSMCs to MMA(III), but not iAs(III), significantly decreased basal and maximal oxygen consumption rates and concomitantly increased compensatory extracellular acidification rates, a proxy of glycolysis. Treatment with MMA(III) significantly increased hydrogen peroxide and superoxide levels compared to iAs(III). Exposure to MMA(III) resulted in significant decreases in mitochondrial ATP, aberrant perinuclear clustering of mitochondria, and decreased mitochondrial content. Mechanistically, we observed that mitochondrial superoxide and hydrogen peroxide contribute to mitochondrial toxicity, as treatment of cells with MnTBAP (a mitochondrial superoxide dismutase mimetic) and catalase significantly reduced mitochondrial respiration deficits and cell death induced by both arsenic compounds. Overall, our data demonstrates that MMA(III) is a mitochondria-specific toxicant that elevates mitochondrial and non-mitochondrial sources of ROS.

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“…This suggests that reactive oxygen species (ROS) originating in mitochondria contribute to the BPD-like injury. Indeed, during chemical toxic stress in vitro , mitochondria-originated ROS are capable of mitochondrial self-oxidation, the event which promotes oxidative injury in the lungs (39,40). Interestingly, in the mitochondria isolated from the brain, hyperoxia also dramatically accelerates mitochondrial ROS production, causing mitochondrial dysfunction secondary to self-oxidative damage (41).…”

Section: Postnatal Causes Of Mitochondrial Dysfunction In the Developmentioning

confidence: 99%

Mitochondrial dysfunction in alveolar and white matter developmental failure in premature infants

Ten

2016

Pediatr Res

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At birth, some organs in premature infants are not developed enough to meet challenges of the extra-uterine life. Although growth and maturation continues after premature birth, postnatal organ development may become sluggish or even arrested, leading to organ dysfunction. There is no clear mechanistic concept of this postnatal organ developmental failure in premature neonates. This review introduces a concept-forming hypothesis: Mitochondrial bioenergetic dysfunction is a fundamental mechanism of organs maturation failure in premature infants. Data collected in support of this hypothesis are relevant to two major diseases of prematurity: white matter injury and broncho-pulmonary dysplasia. In these diseases, totally different clinical manifestations are defined by the same biological process, developmental failure of the main functional units—alveoli in the lungs and axonal myelination in the brain. Although molecular pathways regulating alveolar and white matter maturation differ, proper bioenergetic support of growth and maturation remains critical biological requirement for any actively developing organ. Literature analysis suggests that successful postnatal pulmonary and white matter development highly depends on mitochondrial function which can be inhibited by sublethal postnatal stress. In premature infants, sublethal stress results mostly in organ maturation failure without excessive cellular demise.

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ROS-mediated endoplasmic reticulum stress and mitochondrial dysfunction underlie apoptosis induced by resveratrol and arsenic trioxide in A549 cells

Cited by 103 publications

References 40 publications

The novel resveratrol derivative 3,5-diethoxy-3′,4′-dihydroxy-trans-stilbene induces mitochondrial ROS-mediated ER stress and cell death in human hepatoma cells in vitro

The novel resveratrol derivative 3,5-diethoxy-3′,4′-dihydroxy-trans-stilbene induces mitochondrial ROS-mediated ER stress and cell death in human hepatoma cells in vitro

Monomethylarsonous acid, but not inorganic arsenic, is a mitochondria-specific toxicant in vascular smooth muscle cells

Mitochondrial dysfunction in alveolar and white matter developmental failure in premature infants

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