View in EDS

Effects of dinuclear berenil-platinum(II) complexes on fibroblasts redox status

Saved in:
Bibliographic Details
Title: Effects of dinuclear berenil-platinum(II) complexes on fibroblasts redox status
Authors: Wojciech Łuczaj, Agnieszka Gęgotek, Elżbieta Skrzydlewska, Anna Bielawska, Ewa Ambrożewicz, Krzysztof Bielawski, Agnieszka Markowska
Source: Advances in Medical Sciences. 58:282-291
Publisher Information: Elsevier BV, 2013.
Publication Year: 2013
Subject Terms: 0301 basic medicine, Organoplatinum compounds - pharmacology, Catalase - metabolism, Organoplatinum Compounds, Pikoliny pochodne - farmakologia, Cysplatyna - farmakologia, Antineoplastic agents - pharmacology, Apoptosis, Platinum Compounds, DNA - metabolism, Fibroblasts - drug effects, Antioxidants, Piperazines, high pressure liquid, Cisplatin - pharmacology, Picolines - pharmacology, Stres oksydacyjny, Skin, Chromatography, DNA - metabolizm, Reakcje redoks - wpływ środków chemicznych, Propylamines, Dysmutaza ponadtlenkowa - metabolizm, Blotting, Western bloting, Platinum compounds - pharmacology, Catalase, Linia komórkowa (w hodowli), 3. Good health, Fibroblasty - metabolizm, Picolines, Superoxide dismutase - metabolism, Katalaza - metabolizm, Western, Oxidation-Reduction, Fibroblasty - wpływ środków chemicznych, Reduktaza glutationowa - metabolizm, Chromatografia wysokociśnieniowa w cieczy, Apoptosis - drug effects, Oxidation-reduction - drug effects, Apoptoza - wpływ środków chemicznych, Antineoplastic Agents, Cell Line, Fibroblasts - metabolism, 03 medical and health sciences, Peroksydacja lipidów - wpływ środków chemicznych, Glutathione reductase - metabolism, Humans, Piperazine, Lipid peroxidation - drug effects, Glutathione Peroxidase, Związki platyny - farmakologia, Superoxide Dismutase, Platynoorganiczne związki - farmakologia, DNA, Glutathione peroxidase - metabolism, Fibroblasts, Antioxidants - metabolism, Środki przeciwnowotworowe - farmakologia, Oxidative stress, Antyoksydanty - metabolizm, Peroksydaza glutationowa - metabolizm, Lipid Peroxidation, Cisplatin, Cell line
Description: Platinum(II) complex anticarcinogenic mechanisms are associated with changes in the cellular redox status of cancer as well as healthy cells. Therefore, the goal of the present study was to investigate oxidative modifications in cellular components following fibroblast exposure to novel dinuclear berenil-platinum(II) complexes.ROS levels, antioxidant parameters level/activity, and damage to DNA, lipids, and proteins, including pro-apoptotic and anti-apoptotic factors in human skin fibroblasts following berenil-platinum(II) complex treatments i.e. Pt2(isopropylamine)4(berenil)2, Pt2(piperazine)4(berenil)4, Pt2(2-picoline)4(berenil)2, Pt2(3-picoline)4(berenil)2, and Pt2(4- picoline)4(berenil)2 were examined.Treatment of fibroblasts with platinum(II) complexes has shown that all compounds enhance total ROS and superoxide anion generation as well as change the activity of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase and decrease in the level of non-enzymatic antioxidants (GSH, vitamin C, E and A). Such a situation is conducive to oxidative stress formation and oxidative modifications of cellular macromolecules and to increase in the expression of proapoptotic proteins. Pt2(isopropylamine)4(berenil)2 elicited the most damage, which resulted in oxidative modification of cellular components. The therapeutic use of this complex would cause considerable side effects in patients, therefore the agent lacks drug potential; however Pt2(piperazine)4(berenil)2 and Pt2(2-picoline)4(berenil)2 exhibited reduced redox and increased apoptotic profiles compared to cisplatin.Results of this paper and preliminary data show that Pt2(2-picoline)4(berenil)2 is less dangers than cisplatin to fibroblasts and more disruptive than cisplatin to breast cancer cell metabolism, and therefore it is a promising candidate for use in future anticancer drug strategies.
Document Type: Article
Language: English
ISSN: 1896-1126
DOI: 10.2478/ams-2013-0029
Access URL: https://pubmed.ncbi.nlm.nih.gov/24127544
https://www.sciencedirect.com/science/article/pii/S1896112614602017
https://www.ncbi.nlm.nih.gov/pubmed/24127544
http://www.sciencedirect.com/science/article/pii/S1896112614602017
https://doi.org/10.2478/ams-2013-0029
Rights: Elsevier TDM
Accession Number: edsair.doi.dedup.....21c44a58f7b03cc00331c8cca9680a5f
Database: OpenAIRE
Description
Abstract:Platinum(II) complex anticarcinogenic mechanisms are associated with changes in the cellular redox status of cancer as well as healthy cells. Therefore, the goal of the present study was to investigate oxidative modifications in cellular components following fibroblast exposure to novel dinuclear berenil-platinum(II) complexes.ROS levels, antioxidant parameters level/activity, and damage to DNA, lipids, and proteins, including pro-apoptotic and anti-apoptotic factors in human skin fibroblasts following berenil-platinum(II) complex treatments i.e. Pt2(isopropylamine)4(berenil)2, Pt2(piperazine)4(berenil)4, Pt2(2-picoline)4(berenil)2, Pt2(3-picoline)4(berenil)2, and Pt2(4- picoline)4(berenil)2 were examined.Treatment of fibroblasts with platinum(II) complexes has shown that all compounds enhance total ROS and superoxide anion generation as well as change the activity of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase and decrease in the level of non-enzymatic antioxidants (GSH, vitamin C, E and A). Such a situation is conducive to oxidative stress formation and oxidative modifications of cellular macromolecules and to increase in the expression of proapoptotic proteins. Pt2(isopropylamine)4(berenil)2 elicited the most damage, which resulted in oxidative modification of cellular components. The therapeutic use of this complex would cause considerable side effects in patients, therefore the agent lacks drug potential; however Pt2(piperazine)4(berenil)2 and Pt2(2-picoline)4(berenil)2 exhibited reduced redox and increased apoptotic profiles compared to cisplatin.Results of this paper and preliminary data show that Pt2(2-picoline)4(berenil)2 is less dangers than cisplatin to fibroblasts and more disruptive than cisplatin to breast cancer cell metabolism, and therefore it is a promising candidate for use in future anticancer drug strategies.
ISSN:18961126
DOI:10.2478/ams-2013-0029