Oxidative Stress and Deregulated DNA Damage Response Network in Lung Cancer Patients

Stefanou, Dimitra; Kouvela, Marousa; Stellas, Dimitris; Voutetakis, Konstantinos; Papadodima, Olga; Syrigos, Konstantinos; Souliotis, Vassilis L.

doi:10.3390/biomedicines10061248

Cited by 3 publications

(1 citation statement)

References 49 publications

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“…The progression of carcinogenesis is affected by oxidative stress, inflammation, and apoptosis [ 9 , 10 ]. Oxidative stress is important in the initiation, progression, and invasiveness of lung cancer [ 11 ]. Reactive oxygen species (ROS) are reported to cause DNA damage and mutations in purines, pyrimidines, and oxidate chromatin, causing genomic instability, influencing gene expression, and promoting carcinogenesis and cancer progression [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

The anticarcinogenic effect of eugenol on lung cancer induced by diethylnitrosamine/2-acetylaminofluorene in Wistar rats: insight on the mechanisms of action

et al. 2023

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This study was designed to assess the ameliorative effects of eugenol and to propose the possible mechanisms of action of eugenol in diethylnitrosamine (DENA)/acetylaminofluorene (AAF)-caused lung cancer in Wistar rats. To induce lung cancer, DENA at a dose of 150 mg/kg body weight (b.wt) for 2 weeks were intraperitoneally injected once each week and AAF was administered orally at a dose of 20 mg/kg b.wt. four times each week for the next 3 weeks. DENA/AAF-administered rats were orally supplemented with eugenol at a dose of 20 mg/kg b.wt administered once a day until 17 weeks starting from the 1st week of DENA administration. Lung histological lesions, including sheets of tumor cells, micropapillary adenocarcinoma, and apoptotic cells, resulting from the DENA/AAF dosage, were ameliorated by eugenol treatment. However, a significant drop in the levels of LPO in the lungs and a remarkable rise in GSH content and GPx and SOD activities were observed in DENA/AAF-administered rats treated with eugenol compared with those in DENA/AAF-administered controls. Moreover, in DENA/AAF-administered rats, eugenol supplementation significantly reduced TNF-α and IL-1β levels and mRNA expression levels of NF-κB, NF-κB p65, and MCP-1 but significantly elevated the level of Nrf2. Furthermore, the DENA/AAF-administered rats treated with eugenol exhibited a significant downregulation of Bcl-2 expression levels in addition to a significant upregulation in P53 and Bax expression levels. Otherwise, the administration of DENA/AAF elevated the protein expression level of Ki-67, and this elevation was reversed by eugenol treatment. In conclusion, eugenol has effective antioxidant, anti-inflammatory, proapoptotic, and antiproliferative properties against lung cancer. Graphical abstract

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Section: Introductionmentioning

confidence: 99%

The anticarcinogenic effect of eugenol on lung cancer induced by diethylnitrosamine/2-acetylaminofluorene in Wistar rats: insight on the mechanisms of action

et al. 2023

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Oxidative stress gene signature construction to identify subtypes and prognosis of patients with lung adenocarcinoma

Li,

Qin,

Wang

et al. 2024

Heliyon

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Targeting the DNA Damage Response Machinery for Lung Cancer Treatment

Venugopala

2022

Pharmaceuticals

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Lung cancer is considered the most commonly diagnosed cancer and one of the leading causes of death globally. Despite the responses from small-cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) patients to conventional chemo- and radiotherapies, the current outcomes are not satisfactory. Recently, novel advances in DNA sequencing technologies have started to take off which have provided promising tools for studying different tumors for systematic mutation discovery. To date, a limited number of DDR inhibition trials have been conducted for the treatment of SCLC and NSCLC patients. However, strategies to test different DDR inhibitor combinations or to target multiple pathways are yet to be explored. With the various biomarkers that have either been recently discovered or are the subject of ongoing investigations, it is hoped that future trials would be designed to allow for studying targeted treatments in a biomarker-enriched population, which is defensible for the improvement of prognosis for SCLC and NSCLC patients. This review article sheds light on the different DNA repair pathways and some of the inhibitors targeting the proteins involved in the DNA damage response (DDR) machinery, such as ataxia telangiectasia and Rad3-related protein (ATR), DNA-dependent protein kinase (DNA-PK), and poly-ADP-ribose polymerase (PARP). In addition, the current status of DDR inhibitors in clinical settings and future perspectives are discussed.

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Oxidative Stress and Deregulated DNA Damage Response Network in Lung Cancer Patients

Cited by 3 publications

References 49 publications

The anticarcinogenic effect of eugenol on lung cancer induced by diethylnitrosamine/2-acetylaminofluorene in Wistar rats: insight on the mechanisms of action

The anticarcinogenic effect of eugenol on lung cancer induced by diethylnitrosamine/2-acetylaminofluorene in Wistar rats: insight on the mechanisms of action

Oxidative stress gene signature construction to identify subtypes and prognosis of patients with lung adenocarcinoma

Targeting the DNA Damage Response Machinery for Lung Cancer Treatment

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