Antiproliferative Effect of Acridine Chalcone Is Mediated by Induction of Oxidative Stress

• Published in: Biomolecules (Basel, Switzerland) Vol. 10; no. 2; p. 345
• Main Authors: Takac, Peter, Kello, Martin, Vilkova, Maria, Vaskova, Janka, Michalkova, Radka, Mojzisova, Gabriela, Mojzis, Jan
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 22.02.2020; MDPI
• Subjects: Acetylcysteine; Acridine; Acridines - pharmacology; Antioxidants; Antioxidants - pharmacology; antiproliferative; Apoptosis; Apoptosis - drug effects; Automation; Cancer; Cell cycle; Cell Death - drug effects; Cell growth; Cell Line, Tumor; Chalcone - metabolism; Chalcone - pharmacology; chalcones; Chalcones - pharmacology; Colon cancer; Deoxyribonucleic acid; DNA; DNA damage; Flow cytometry; Free radicals; Humans; Hypotheses; Immunoglobulins; Kinases; MAP kinase; Metabolism; Mitochondrial DNA; NMR; Nuclear magnetic resonance; Oxidants; Oxidative stress; Oxidative Stress - drug effects; Oxidative Stress - physiology; Phosphorylation; Proteins; Reactive nitrogen species; Reactive oxygen species; Reactive Oxygen Species - metabolism; Signal transduction; Signal Transduction - drug effects; Statistical analysis; Superoxide; United Kingdom > UK; United States > US; Germany; chalcones; antiproliferative; oxidative stress
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom10020345

Chalcones are naturally occurring phytochemicals with diverse biological activities including antioxidant, antiproliferative, and anticancer effects. Some studies indicate that the antiproliferative effect of chalcones may be associated with their pro-oxidant effect. In the present study, we evaluated contribution of oxidative stress in the antiproliferative effect of acridine chalcone 1C ((2 E)-3-(acridin-9-yl)-1-(2,6-dimethoxyphenyl)prop-2-en-1-one) in human colorectal HCT116 cells. We demonstrated that chalcone 1C induced oxidative stress via increased reactive oxygen/nitrogen species (ROS/RNS) and superoxide production with a simultaneous weak adaptive activation of the cellular antioxidant defence mechanism. Furthermore, we also showed chalcone-induced mitochondrial dysfunction, DNA damage, and apoptosis induction. Moreover, activation of mitogen activated phosphokinase (MAPK) signalling pathway in 1C-treated cancer cells was also observed. On the other hand, co-treatment of cells with strong antioxidant, -acetyl cysteine (NAC), significantly attenuated all of the above-mentioned effects of chalcone 1C, that is, decreased oxidant production, prevent mitochondrial dysfunction, DNA damage, and induction of apoptosis, as well as partially preventing the activation of MAPK signalling. Taken together, we documented the role of ROS in the antiproliferative/pro-apoptotic effects of acridine chalcone 1C. Moreover, these data suggest that this chalcone may be useful as a promising anti-cancer agent for treating colon cancer.