Can CYP1A1 siRNA be an effective treatment for lung cancer?

Mohammed, Kulthum Karama; Shervington, Amal

doi:10.2478/s11658-007-0050-x

Cited by 5 publications

(3 citation statements)

References 26 publications

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“…However, under certain conditions, this enzyme will catalyze the bioactivation of compounds that may react with macromolecules, which can cause the mutagenesis process (Barber et.al., 2008). According to Mohammed and Shervingto (2008), CYP1A1 is an extrahepatic enzyme Glyco-ebov catalyzing the bioactivation of polyaromatic hydrocarbons (PAH) which are abundant in tobacco smoke. It can cause mutagens and carcinogens.…”

Section: Discussionmentioning

confidence: 99%

Lentiviral shRNA Construction in Gene Therapy for Knock Down CYPIA1, and YWHAZ gene in Lung Cancer

2021

Journal of Biological Science and Education

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A. IntroductionLung cancer or lung carcinoma is a malignant lung tumor caused by uncontrolled cell growth of lung tissue (Mustafa, et al. 2016). Based on data presented by WHO (2019), lung cancer is a disease that is in the top 10 causes of death globally, to be precise it is in the 6 th top rank after ischaemic heart disease, stroke, chronic obstructive pulmonary disease, lower respiratory infections, and neonatal conditions. The risk factors include smoking both active and passive, exposure to radon gas, asbestos, air pollution, and genetic factors. Smoking is the main cause of lung cancer (Mustafa, et al., 2016). Smoking can cause CYP1A1 and YWHAZ genes expressed in the lungs. One solution that can be applied to reduce death cases of lung cancer is the use of gene therapy.Gene therapy for lung cancer is focused on the knock-down of expressed CYP1A1 and YWHAZ genes. They are important gene causing growth lung cell abnormally. CYP1A1 converts tobacco combustion products containing PAHs into reactive metabolites that may be involved in the initiation of carcinogenesis. Meanwhile, YWHAZ is one of the hub genes with the highest level of presence. The encoded proteins are involved in many vital cellular processes such as

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Section: Discussionmentioning

confidence: 99%

Lentiviral shRNA Construction in Gene Therapy for Knock Down CYPIA1, and YWHAZ gene in Lung Cancer

2021

Journal of Biological Science and Education

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“…21 A positive correlation between upregulated expression of human telomerase reverse transcriptase (hTERT), the telomerase catalytic subunit and CYP1A1 was observed in human lung cancer, indirectly suggesting that CYP1A1 might be associated with telomere-telomerase function. 22 Based on these findings, we hypothesize that MLT may exert its protective function in vascular aging of atherosclerosis through targeting CYP1A1-mediated telomeretelomerase function. We aim to verify this hypothesis by conducting a series of in vivo and in vitro experiments.…”

Section: Introductionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Melatonin Alleviates Age-Associated Endothelial Injury of Atherosclerosis via Regulating Telomere Function

Xie¹,

D²,

Zhang³

2021

JIR

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Background Atherosclerosis is an aging-related disease, partly attributed to telomerase dysfunction. This study aims to investigate whether telomere dysfunction-related vascular aging is involved in the protection mechanism of melatonin (MLT) in atherosclerosis. Methods Young and aged ApoE −/− mice were used to establish atherosclerotic mice model. H&E staining and immunofluorescence assay were performed to detect endothelial cell injury and apoptosis. Inflammatory cytokines and oxidative stress-related factors were determined using corresponding commercial assay kits. Telomerase activity was detected by TRAP assay, and SA-β-gal staining was conducted to evaluate cellular senescence. HUVECs were treated with H 2 O 2 for 1 h to induce senescence. Western blot was performed to measure protein expression. Results An obvious vascular endothelial injury, reflected by excessive production of inflammatory cytokines, elevated ROS, MDA and SOD levels, and more apoptotic endothelial cells, was found in atherosclerotic mice, especially in aged mice, which were then greatly suppressed by MLT. In addition, telomere dysfunction and senescence occurred in atherosclerosis, especially in aged mice, while MLT significantly alleviated the conditions. CYP1A1, one of the targeted genes of MLT, was verified to be upregulated in atherosclerotic mice but downregulated by MLT. Furthermore, H 2 O 2 induced a senescence model in HUVECs, which was accompanied with a remarkably increased cell viability loss and apoptosis rate, and a downregulated telomerase activity of HUVECs, and this phenomenon was strengthened by RHPS4, an inhibitor of telomerase activity. However, MLT could partly abolish these changes in H 2 O 2 - and RHPS4-treated HUVECs, demonstrating that MLT alleviated vascular endothelial injury by regulating senescence and telomerase activity. Conclusions Collectively, this study provided evidence for the protective role of MLT in atherosclerosis through regulating telomere dysfunction-related vascular aging.

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RNA Interference for Cancer Therapy

Cheng

Qin

2009

Pharmaceutical Perspectives of Cancer Therapeutics

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Can CYP1A1 siRNA be an effective treatment for lung cancer?

Cited by 5 publications

References 26 publications

Lentiviral shRNA Construction in Gene Therapy for Knock Down CYPIA1, and YWHAZ gene in Lung Cancer

Lentiviral shRNA Construction in Gene Therapy for Knock Down CYPIA1, and YWHAZ gene in Lung Cancer

Melatonin Alleviates Age-Associated Endothelial Injury of Atherosclerosis via Regulating Telomere Function

RNA Interference for Cancer Therapy

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