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Open AccessArticle

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

1
Department of Pharmacology, Faculty of Medicine, Pavol Jozef Safarik University, 040 11 Kosice, Slovakia
2
Institute of Human and Clinical Pharmacology, University of Veterinary Medicine and Pharmacy, 041 81 Kosice, Slovakia
3
Department of Organic Chemistry, Faculty of Science, Pavol Jozef Safarik University, 040 01 Kosice, Slovakia
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Department of Medical and Clinical Biochemistry, Faculty of Medicine, Pavol Jozef Safarik University, 040 01 Kosice, Slovakia
5
Department of Experimental Medicine, Faculty of Medicine, Pavol Jozef Safarik University, 040 01 Kosice, Slovakia
*
Authors to whom correspondence should be addressed.
Biomolecules 2020, 10(2), 345; https://doi.org/10.3390/biom10020345
Received: 18 December 2019 / Revised: 14 February 2020 / Accepted: 19 February 2020 / Published: 22 February 2020
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, N-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. View Full-Text
Keywords: chalcones; antiproliferative; oxidative stress chalcones; antiproliferative; oxidative stress
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MDPI and ACS Style

Takac, P.; Kello, M.; Vilkova, M.; Vaskova, J.; Michalkova, R.; Mojzisova, G.; Mojzis, J. Antiproliferative Effect of Acridine Chalcone Is Mediated by Induction of Oxidative Stress. Biomolecules 2020, 10, 345. https://doi.org/10.3390/biom10020345

AMA Style

Takac P, Kello M, Vilkova M, Vaskova J, Michalkova R, Mojzisova G, Mojzis J. Antiproliferative Effect of Acridine Chalcone Is Mediated by Induction of Oxidative Stress. Biomolecules. 2020; 10(2):345. https://doi.org/10.3390/biom10020345

Chicago/Turabian Style

Takac, Peter; Kello, Martin; Vilkova, Maria; Vaskova, Janka; Michalkova, Radka; Mojzisova, Gabriela; Mojzis, Jan. 2020. "Antiproliferative Effect of Acridine Chalcone Is Mediated by Induction of Oxidative Stress" Biomolecules 10, no. 2: 345. https://doi.org/10.3390/biom10020345

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