Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.788963
Title: The possible links between COPD and lung cancer : cellular and mitochondrial function in airway epithelial cells
Author: Thangboonjit, Weerawon
ISNI:       0000 0004 8499 4638
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2019
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Abstract:
Cigarette smoke (CS) is a major risk factor for both COPD and lung cancer and many lung cancer patients have COPD. CS-derived oxidant exposure in airway epithelial cells leads to abnormal function. Persistent inflammation in COPD together with mutations and dysregulated cell cycle contributes to lung cancer development. Mitochondria are the hub of bioenergetics, reactive oxygen species (ROS) production and intracellular signalling pathways. The role of mitochondria in the development of lung cancer in COPD is not widely investigated. We hypothesised that mitochondrial dysfunction causes some COPD patients to develop lung cancer. Treatment of bronchial epithelial cell line (BEAS-2B) with hydrogen peroxide (H2O2) caused mitochondrial function alteration and apoptosis. Interleukin (IL)-1β-induced proliferation and inflammation was greater when co-treated with H2O2. N-acetyl cysteine had a greater protective effect than mitochondrial-targeted antioxidants. The effects of mitochondrial-directed antioxidants were also investigated in BEAS-2B, normal primary bronchial epithelial cells (NHBE) and the lung cancer cell line (A549). At baseline, A549 showed lower mitochondrial membrane potential and higher mitochondrial superoxide and respiration spare capacity. Mitochondrial protection by antioxidants in these cell types was unclear as H2O2 minimally affected the mitochondrial parameters and cell functions. Gene Set Variation Analysis (GSVA) revealed that oxidative phosphorylation (OXPHOS) and glycolysis pathway signatures in lung cancer patients were related to smoking status. Matched normal-tumour pairs showed significantly higher glycolytic gene expression in tumour whereas higher mitochondrial protein (NDUFA9) expression was detected in background tissue from smokers compared with tumour tissue in COPD patients suggesting an early OXPHOS compensatory mechanism in background tissue and glycolytic switching in the tumour. Background and tumour tissues suggested defects in mitochondrial structure in COPD. This study provides an initial insight into how changes in mitochondria and metabolic pathways could link COPD and lung cancer and has clinical implications for carcinogenesis prevention by treating COPD patients.
Supervisor: Adcock, Ian ; Mumby, Sharon Sponsor: Mahāwitthayālai Mahidon
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.788963  DOI:
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