Wood dust exposure induces cell transformation through EGFR-mediated OGG1 inhibition

Staffolani, Sara; Manzella, Nicola; Strafella, Elisabetta; Nocchi, Linda; Bracci, Massimo; Ciarapica, Veronica; Amati, Monica; Rubini, Corrado; Re, Massimo; Pugnaloni, Armanda; Pasquini, Ernesto; Tarchini, Paolo; Valentino, Matteo; Tomasetti, Marco; Santarelli, Lory

doi:10.1093/mutage/gev007

Cited by 12 publications

(8 citation statements)

References 38 publications

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“…17 OGG1 has also been shown to affect the cell transformation in wood dust exposure-induced or asbestos-induced pulmonary fibrosis in mice. 18,19 Whole transcriptome analysis showed that OGG1 plays an important role in tissue remodeling, and affects the actin cytoskeleton, the ECM, cell adhesion, cadherin, and cell junctions. 20 In this study, we focused on the mechanisms by which OGG1 affects TGF-β1-driven repair using both in vitro and in vivo approaches.…”

Section: Introductionmentioning

confidence: 99%

8‐Oxoguanine DNA glycosylase modulates the cell transformation process in pulmonary fibrosis by inhibiting Smad2/3 and interacting with Smad7

et al. 2020

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The DNA repair enzyme 8‐oxoguanine DNA glycosylase‐1 (OGG1) is involved in early embryonic development, as well as in multiple conditions, including cardiac fibrosis, diabetes, and neurodegenerative diseases. But, function of OGG1 in pulmonary fibrosis was not entirely clear. In this study, we identified a novel function of OGG1 in the cell transformation process in pulmonary fibrosis. We demonstrated that OGG1 and Smad7 co‐localize and interact in A549 cells. Bleomycin‐induced pulmonary fibrosis was established in wild‐type (WT) and Ogg1‐/‐ mice. Upon treatment with transforming growth factor (TGF)‐β1, increased OGG1 expression was observed in WT mice with pulmonary fibrosis as well as in A549 cells, MRC‐5 cells, and primary rat type II alveolar epithelial cells. The increased expression of OGG1 promoted cell migration, while OGG1 depletion decreased migration ability. Expression of the transformation‐associated markers vimentin and alpha‐smooth muscle actin were also affected by OGG1. We also observed that OGG1 promoted TGF‐β1‐induced cell transformation and activated Smad2/3 by interacting with Smad7. The interaction between OGG1 and the TGF‐β/Smad axis modulates the cell transformation process in lung epithelial cells and fibroblasts. Moreover, we demonstrated that Ogg1 deficiency relieved pulmonary fibrosis in bleomycin‐treated mice. Ogg1 knockout decreased the bleomycin‐induced expression of Smad7 and phosphorylation of Smad2/3 in mice. These findings suggest that OGG1 has multiple biological functions in the pathogenesis of pulmonary fibrosis.

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Section: Introductionmentioning

confidence: 99%

8‐Oxoguanine DNA glycosylase modulates the cell transformation process in pulmonary fibrosis by inhibiting Smad2/3 and interacting with Smad7

et al. 2020

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“…demonstrated that activation of EGFR/AKT/mTOR pathway induced the phosphorylation and subsequent inactivation of tuberin thus resulting in inhibition of OGG1 expression, consistent with results obtained by Habib. Therefore, the reduced expression of OGG1 determined DNA lesion accumulation, cell survival and proliferation ( 49 ).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, a link between EGFR signaling and DNA repair mechanisms has been shown previously ( 47 , 48 ). Staffolani and colleagues demonstrated that in a human lung cell line, EGFR down-regulates wood-dust-induced OGG1 expression via AKT ( 49 ). However, to date, correlation between the BER and ErbB systems in gastric cancer has not been investigated.…”

Section: Introductionmentioning

confidence: 99%

Effects of H2O2 Treatment Combined With PI3K Inhibitor and MEK Inhibitor in AGS Cells: Oxidative Stress Outcomes in a Model of Gastric Cancer

et al. 2022

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Gastric cancer is worldwide the fifth and third cancer for incidence and mortality, respectively. Stomach wall is daily exposed to oxidative stress and BER system has a key role in the defense from oxidation-induced DNA damage, whilst ErbB receptors have important roles in the pathogenesis of cancer. We used AGS cells as an aggressive gastric carcinoma cell model, treated with H2O2 alone or combined with ErbB signaling pathway inhibitors, to evaluate the effects of oxidative stress in gastric cancer, focusing on the modulation of ErbB signaling pathways and their eventual cross-talk with BER system. We showed that treatment with H2O2 combined with PI3K/AKT and MEK inhibitors influenced cell morphology and resulted in a reduction of cancer cell viability. Migration ability was reduced after H2O2 treatment alone or combined with MEK inhibitor and after PI3K/AKT inhibitor alone. Western blotting analysis showed that oxidative stress stimulated EGFR pathway favoring the MAPKs activation at the expense of PI3K/AKT pathway. Gene expression analysis by RT-qPCR showed ErbB2 and OGG1 increase under oxidative stress conditions. Therefore, we suggest that in AGS cells a pro-oxidant treatment can reduce gastric cancer cell growth and migration via a different modulation of PI3K and MAPKs pathways. Moreover, the observed ErbB2 and OGG1 induction is a cellular response to protect the cells from H2O2-induced cell death. In conclusion, to tailor specific combinations of therapies and to decide which strategy to use, administration of a chemotherapy that increases intracellular ROS to toxic levels, might not only be dependent on the tumor type, but also on the molecular targeting therapy used.

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“…After 24 h or 48 h of treatment, 10 µL of MTT (5 mg/mL in PBS) was added to each well and the plate was incubated again for 3 h at 37 °C in incubator. Next, medium was removed, 200 µL of isopropanol was added, and the absorbance was read at 595 nm [ 73 ]. Cell viability rate was calculated following the formula: cell viability (%) = (average OD value of AITC-treated cells/average OD value of control cells) × 100.…”

Section: Methodsmentioning

confidence: 99%

Allyl Isothiocyanate Exhibits No Anticancer Activity in MDA-MB-231 Breast Cancer Cells

Sayeed

Bracci

Ciarapica

et al. 2018

IJMS

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It was reported recently that allyl isothiocyanate (AITC) could inhibit various types of cancer cell growth. In the present study, we further investigated whether AITC could inhibit the growth of human breast cancer cells. Unexpectedly, we found that AITC did not inhibit, rather slightly promoted, the proliferation of MDA-MB-231 breast cancer cells, although it did have inhibitory effect on MCF-7 breast cancer cells. Cytofluorimetric analysis revealed that AITC (10 µM) did not induce apoptosis and cell cycle arrest in MDA-MB-231 cells. In addition, AITC significantly (p < 0.05) increased the expression of BCL-2 and mTOR genes and Beclin-1 protein in MDA-MB-231 cells. No significant changes in expression of PRKAA1 and PER2 genes, Caspase-8, Caspase-9, PARP, p-mTOR, and NF-κB p65 proteins were observed in these AITC-treated cells. Importantly, AITC displayed cytotoxic effect on MCF-10A human breast epithelial cell line. These observations suggest that AITC may not have inhibitory activity in MDA-MB-231 breast cancer cells. This in vitro study warrants more preclinical and clinical studies on the beneficial and harmful effects of AITC in healthy and cancer cells.

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Wood dust exposure induces cell transformation through EGFR-mediated OGG1 inhibition

Cited by 12 publications

References 38 publications

8‐Oxoguanine DNA glycosylase modulates the cell transformation process in pulmonary fibrosis by inhibiting Smad2/3 and interacting with Smad7

8‐Oxoguanine DNA glycosylase modulates the cell transformation process in pulmonary fibrosis by inhibiting Smad2/3 and interacting with Smad7

Effects of H2O2 Treatment Combined With PI3K Inhibitor and MEK Inhibitor in AGS Cells: Oxidative Stress Outcomes in a Model of Gastric Cancer

Allyl Isothiocyanate Exhibits No Anticancer Activity in MDA-MB-231 Breast Cancer Cells

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