Polychlorinated-biphenyl-induced oxidative stress and cytotoxicity can be mitigated by antioxidants after exposure

Zhu, Yueming; Kalen, Amanda L.; Li, Ling; Lehmler, Hans‐Joachim; Robertson, Larry W.; Goswami, Prabhat C.; Spitz, Douglas R.; Aykin-Burns, Nūkhet

doi:10.1016/j.freeradbiomed.2009.09.024

Cited by 77 publications

(85 citation statements)

References 39 publications

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“…As such, pre-treatment with antioxidants is anticipated to suppress ROS-mediated activation of AhR-signaling in 4-ClBQ treated cells. Pre-treatment with antioxidants (NAC; superoxide dismutase and catalase) has been shown to suppress 4-ClBQ induced increase in ROS levels and toxicity in HaCaT, and human mammary and prostate epithelial cells (Venkatesha et al, 2008; Xiao et al, 2013; Zhu et al, 2009). Pre-treatment with NAC significantly suppressed 4-ClBQ-induced increase in CYP1A1 mRNA expression (Fig.…”

Section: Discussionmentioning

confidence: 99%

Ligand-independent activation of aryl hydrocarbon receptor signaling in PCB3-quinone treated HaCaT human keratinocytes

et al. 2015

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Aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that plays a critical role in metabolism, cell proliferation, development, carcinogenesis, and xenobiotic response. In general, dioxin-like polychlorinated biphenyls (PCBs) exhibit a ligand-dependent activation of AhR-signaling. Results from this study show that a quinone-derivative (1-(4-Chlorophenyl)-benzo-2,5-quinone; 4-ClBQ) of a non-dioxin like PCB (PCB3) also activates AhR-signaling. Treatments of HaCaT human keratinocytes with 4-ClBQ and dioxin-like PCB126 significantly increased AhR-target gene expression, CYP1A1 mRNA and protein levels. 4-ClBQ-induced increase CYP1A1 expression was associated with an increase in the nuclear translocation of AhR protein as well as an increase in the luciferase-reporter activity of a human CYP1A1 xenobiotic response element (XRE). 6,2′,4′-trimethoxyflavone (TMF), a well-characterized AhR-ligand antagonist significantly suppressed PCB126-induced increase in CYP1A1 expression, while the same treatment did not suppress 4-ClBQ-induced increase in CYP1A1 expression. However, siRNA-mediated down-regulation of AhR significantly inhibited 4-ClBQ-induced increase in CYP1A1 expression, suggesting that AhR mediates 4-ClBQ-induced increase in CYP1A1 expression. Interestingly, treatment with the antioxidant N-acetyl-L-cysteine significantly suppressed 4-ClBQ-induced increase in CYP1A1 expression. Furthermore, CYP1A1 expression also increased in cells treated with hydrogen peroxide. These results demonstrate that a ligand-independent and oxidative stress dependent pathway activates AhR-signaling in 4-ClBQ treated HaCaT cells. Because AhR signaling is believed to mediate xenobiotics response, our results may provide a mechanistic rationale for the use of antioxidants as effective countermeasure to environmental pollutant-induced adverse health effects.

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Section: Discussionmentioning

confidence: 99%

Ligand-independent activation of aryl hydrocarbon receptor signaling in PCB3-quinone treated HaCaT human keratinocytes

et al. 2015

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“…MFI data was then normalized to control for each group at each respective time point, as indicated. 5, 14 …”

Section: Methodsmentioning

confidence: 99%

Antioxidant inhibition of steady-state reactive oxygen species and cell growth in neuroblastoma

Zhu

Paul

Lee

et al. 2015

Surgery

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Background Reactive oxygen species (ROS) contributes to adult tumorigenesis; however, their roles in pediatric solid tumors are unknown. Here, we sought to define the steady-state ROS levels in neuroblastoma and examine whether aggressive cellular behavior, which may predict treatment failure, is regulated by ROS. Methods Neuroblastoma sections were assessed for 4-hydroxynonenal (4HNE), which represents intracellular lipid peroxidation, a byproduct of elevated ROS. Human neuroblastoma cell lines, MYCN-amplified BE(2)-C and MYCN-non-amplified SK-N-SH, were examined for our study. Superoxide and hydroperoxide oxidation products were detected by staining for DHE and CDCFH2, using the oxidation-insensitive analog CDCF as a negative control. Cells were treated with N-acetylcysteine (NAC; 10 mM) daily for 5 d and analyzed. Results Higher expression of 4HNE was observed in undifferentiated tumor sections as compared to benign differentiated tumors. Interestingly, increased levels of ROS were detected in MYCN-amplified BE(2)-C cells. Moreover, GRP-R-induced ROS production stimulated upregulation of the HIF-1α/VEGF pathway and an increase in cell growth. Antioxidant NAC decreased HIF-1α/VEGF expression, inhibited BE(2)-C cell growth. Conclusion . We report a novel observation that shifting the redox balance toward higher ROS results in more aggressive neuroblastoma phenotype. Our data suggest that ROS plays a critical role in refractory neuroblastoma.

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“…Regarding endometrial cancer, molecular epidemiological studies have shown how the activity of superoxide dismutase (SOD) would be lower in the endometrial cancer tissue than in the normal endometrium [43,44] and PCBs have been recently showed to activate the enzymatic activity of SOD 1 in endometrial cancer cells [45] as shown in a previous study where PCBs enhanced the activity of SOD both in MCF-10A human breast cells and RWPE-1 human prostate epithelial cells [46]. …”

Section: Polychlorinated Biphenyls and Endometrial Cancermentioning

confidence: 99%

Endocrine Disrupting Chemicals and Endometrial Cancer: An Overview of Recent Laboratory Evidence and Epidemiological Studies

Mallozzi¹,

Leone²,

Manurita³

et al. 2017

IJERPH

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Background: Although exposure to endocrine disruptor compounds (EDCs) has been suggested as a contributing factor to a range of women’s health disorders including infertility, polycystic ovaries and the early onset of puberty, considerable challenges remain in attributing cause and effect on gynaecological cancer. Until recently, there were relatively few epidemiological studies examining the relationship between EDCs and endometrial cancer, however, in the last years the number of these studies has increased. Methods: A systematic MEDLINE (PubMed) search was performed and relevant articles published in the last 23 years (from 1992 to 2016) were selected. Results: Human studies and animal experiments are confirming a carcinogenic effect due to the EDC exposure and its carcinogenesis process result to be complex, multifactorial and long standing, thus, it is extremely difficult to obtain the epidemiological proof of a carcinogenic effect of EDCs for the high number of confusing factors. Conclusions: The carcinogenic effects of endocrine disruptors are plausible, although additional studies are needed to clarify their mechanisms and responsible entities. Neverthless, to reduce endocrine disruptors (ED) exposure is mandatory to implement necessary measures to limit exposure, particularly during those periods of life most vulnerable to the impact of oncogenic environmental causes, such as embryonic period and puberty.

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Polychlorinated-biphenyl-induced oxidative stress and cytotoxicity can be mitigated by antioxidants after exposure

Cited by 77 publications

References 39 publications

Ligand-independent activation of aryl hydrocarbon receptor signaling in PCB3-quinone treated HaCaT human keratinocytes

Ligand-independent activation of aryl hydrocarbon receptor signaling in PCB3-quinone treated HaCaT human keratinocytes

Antioxidant inhibition of steady-state reactive oxygen species and cell growth in neuroblastoma

Endocrine Disrupting Chemicals and Endometrial Cancer: An Overview of Recent Laboratory Evidence and Epidemiological Studies

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