Anti-cancer effects of 3,5-dimethylaminophenol in A549 lung cancer cells

• Published in: PloS one Vol. 13; no. 10; p. e0205249
• Main Authors: Lin, Pei-Ying, Chang, Yu-Jung, Chen, Yu-Chen, Lin, Chin-Hung, Erkekoglu, Pinar, Chao, Ming-Wei, Tseng, Chia-Yi
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 11.10.2018; Public Library of Science (PLoS)
• Subjects: A549 Cells; Acetylcysteine; Acetylcysteine - pharmacology; Aminophenols - pharmacology; Aminophenols - therapeutic use; Animals; Anticancer properties; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Antioxidants; Apoptosis; Apoptosis - drug effects; Bax protein; Bcl-2 protein; Biocompatibility; Biology and Life Sciences; c-Myc protein; Cancer; Cancer therapies; Carcinogenesis - drug effects; Carcinogens; Caspase; Caspase-3; Cell cycle; Cell migration; Cell Proliferation - drug effects; Chemotherapy; Chen Chen; Cytochrome; Cytochrome c; Cytochromes; Cytotoxicity; Deoxyribonucleic acid; DNA; DNA damage; DNA Damage - drug effects; Enzymatic activity; Female; Fibroblasts; Free Radical Scavengers - pharmacology; Humans; Lipid peroxidation; Lipids; Lung cancer; Lung diseases; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Medicine and Health Sciences; Metastasis; Mice; Mice, Nude; Myc protein; Nanotechnology; Non-small cell lung carcinoma; Outdoor air quality; Oxidation; Oxidative stress; Oxidative Stress - drug effects; p53 Protein; Peroxidation; Proteins; Reactive Oxygen Species - metabolism; Redox properties; Research and Analysis Methods; Superoxide; Toxicity; Tumors; Wood preservatives; Xenograft Model Antitumor Assays; Taiwan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0205249

Exposure to 3,5-dimethylaminophenol (3,5-DMAP), the metabolite of the 3-5-dimethylaniline, was shown to cause high levels of oxidative stress in different cells. The aim of the present work was to observe whether this metabolite can lead to cytotoxicity, oxidative stress, DNA damage and cell cycle changes in non-small cell lung cancer A549 cells. 3,5-DMAP caused a dose-dependent increase in cytotoxicity, generation of superoxide (O2-.), inductions in the enzyme activities orchestrating cellular antioxidant balance, increases in lipid peroxidation as well as DNA damage. However, 3,5-DMAP showed significantly lower cytotoxicity towards human lung fibroblast (HLF) cells. 3,5-DMAP also led to molecular events, like inducing apoptotic markers (ie. p53, Bad, Bax and cytochrome c); decreasing anti-apoptotic proteins (Bcl-2) and alterations in cell cycle. Our findings indicate that the cytotoxicity caused by this particular alkylaniline metabolite led to initiation of caspase 3-mediated apoptosis. Furthermore, 3,5-DMAP attenuated carcinogenic properties like migration capacity of A549 cells and eventually inhibited growth of A549 cells in an in vivo mouse model. Tumor sections showed that 3,5-DMAP down-regulated c-Myc expression but up-regulated p53 and cytochrome c, all of which might result in tumor growth arrest. Co-treatment with N-acetylcysteine provided reductions in cytotoxicity and positively modulated genetic events induced by 3,5-DMAP in A549 cells. In conclusion, our findings demonstrate 3,5-DMAP may be a potential anti-cancer drug in cancer, due to its self redox cycling properties.