ArticleJournal of experimental & clinical cancer research : CR2013
Targeting 3-phosphoinositide-dependent protein kinase 1 by N-acetyl-cysteine through activation of peroxisome proliferators activated receptor alpha in human lung cancer cells, the role of p53 and p65.
Article in Journal of experimental & clinical cancer research : CR, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- Photodynamic Therapy and Dietary Antioxidants: A Dual Strategy for Genome Stability and DNA Damage Repair.Cancer medicine · 2025Review
- Construction of an anoikis-associated lncRNA-miRNA-mRNA network reveals the prognostic role of β-elemene in non-small cell lung cancer.Scientific reports · 2023Article
- 3-Phosphoinositide-dependent kinase 1 drives acquired resistance to osimertinib.Communications biology · 2023Article
- Differentiation-related genes in tumor-associated macrophages as potential prognostic biomarkers in non-small cell lung cancer.Frontiers in immunology · 2023Article
- Review
- Role of Dietary Antioxidants in p53-Mediated Cancer Chemoprevention and Tumor Suppression.Oxidative medicine and cellular longevity · 2021Review
- Glioma Stem-Like Cells and Metabolism: Potential for Novel Therapeutic Strategies.Frontiers in oncology · 2021Review
- Sestrin2 Expression Has Regulatory Properties and Prognostic Value in Lung Cancer.Journal of personalized medicine · 2020Article
- Combined treatment with N-acetylcysteine and gefitinib overcomes drug resistance to gefitinib in NSCLC cell line.Cancer medicine · 2020Article
- Apoptosis and oxidative stress as relevant mechanisms of antitumor activity and genotoxicity of ZnO-NPs alone and in combination with N-acetyl cysteine in tumor-bearing mice.International journal of nanomedicine · 2019Article
- PPARα gene is a diagnostic and prognostic biomarker in clear cell renal cell carcinoma by integrated bioinformatics analysis.Journal of Cancer · 2019Article
- Peroxisome proliferator-activated receptors (PPARs) are potential drug targets for cancer therapy.Oncotarget · 2017Review
- PPAR-γ Agonists As Antineoplastic Agents in Cancers with Dysregulated IGF Axis.Frontiers in endocrinology · 2017Review
- PPARα induces cell apoptosis by destructing Bcl2.Oncotarget · 2015Article
- Bromelain and N-acetylcysteine inhibit proliferation and survival of gastrointestinal cancer cells in vitro: significance of combination therapy.Journal of experimental & clinical cancer research : CR · 2014Article
- The inhibitory effects of extracellular ATP on the growth of nasopharyngeal carcinoma cells via P2Y2 receptor and osteopontin.Journal of experimental & clinical cancer research : CR · 2014Article
- Repression of phosphoinositide-dependent protein kinase 1 expression by ciglitazone via Egr-1 represents a new approach for inhibition of lung cancer cell growth.Molecular cancer · 2014Article
- p38α MAPK-mediated induction and interaction of FOXO3a and p53 contribute to the inhibited-growth and induced-apoptosis of human lung adenocarcinoma cells by berberine.Journal of experimental & clinical cancer research : CR · 2014Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundN-Acetyl-Cysteine (NAC), a natural sulfur-containing amino acid derivative, and peroxisome proliferators activated receptor alpha (PPARα) ligand have been shown to have anticancer properties. However, the mechanisms by which these agents inhibit human non-small cell lung carcinoma (NSCLC) cell growth have not been well elucidated.
methodsSmall interfering RNAs (siRNAs) were used to knockdown 3-phosphoinositide-dependent protein kinase 1 (PDK1), PPARα, p65 and p53 genes; Western Blot was performed to detect the protein expression of PDK1, PPARα, p65 and p53; Cell viability and MTT assays were carried out to determine the cell proliferation; Transient transfection and Dual-Luciferase Reporter assays were used to transfect siRNAs or exogenous expression vectors, and to measure the gene promoter activity.
resultsWe showed that NAC inhibited NSCLC cell proliferation through reduction of PDK1 expression. NAC also induced the protein expression of PPARα. While PPARα ligand enhanced, PPARα antagonist and siRNA abrogated the effect of NAC on PDK1 promoter activity, protein expression and cell growth. Overexpression of PDK1 diminished the inhibitory effect of NAC on cell proliferation. NAC induced p53 and reduced p65 protein expression through activation of PPARα. Silencing of p53 and overexpression of p65 blocked the effect of NAC on PDK1 promoter activity and protein expression.
conclusionOur results show that NAC inhibits PDK1 expression through PPARα-mediated induction of p53 and inhibition of p65 protein expression. PPARα ligand enhances the effect of NAC. This ultimately inhibits NSCLC cell growth. This study unveils a novel mechanism by which NAC in combination with PPARα ligand inhibits growth of human lung carcinoma cells.
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