RESEARCH ARTICLE


Effect of resveratrol and its hydroxylated analogues on proliferation and apoptosis of two cervix cancer derived cancer cell lines. The role of mitochondrial superoxide dismutase



Hanna Piotrowska1, Malgorzata Kucinska1, Marcin Wierzchowski2, Urszula Kazmierczak-Majchrzak3, Marek Murias1, *
1 Department of Toxicology, Poznan University of Medical Sciences, Poznan, Poland
2 Department of Chemical Technology of Drugs, Poznan University of Medical Sciences, Poznan, Poland
3 Department of Cancer Immunology, Poznan University of Medical Sciences at GreatPoland Cancer Center, Poland


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© Piotrowska; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Department of Toxicology, Poznan University of Medical Sciences, ul. Dojazd 30, 60-631 Poznań, Poland; Tel: +48 61 8472081; Fax: +48 61 8470721; E-mail: marek.murias@ump.edu.pl


Abstract

The naturally occurring polyphenol resveratrol (3,4',5-trihydroxy-stilbene, 3,4',5-THS, RES) has been shown as a chemopreventive and proapototic agent. Resveratrol is extensively metabolized by CYP450 enzymes. The monohydroxylation of resveratrol is catalyzed by CYP1B1 to form 3,3',4',5-THS (piceatannol), a metabolite with higher anticancer activity and stronger antioxidant properties. It was hypothesized that RES analogues (HHRAs) possessing more than 3 hydroxyl groups may act stronger against cancer cells than RES due to reactive oxygen species formed in redox-cycling reactions. In order to investigate a structure-activity relationship between pro/antioxidant properties and cytotoxicity, the HHRAs with at least 2 phenolic groups in neighborhood- 3,4,4',5-HS and 3,3',4,4',5,5'-HS were synthesized. In the present study we tested this hypothesis in a cell culture model using HeLa and C33A cancer cell lines. The results of our experiments support a hypothesis that MnSOD overexpressing HeLa cells are much more resistant to superoxide generating HHRAs than C33A cells.

Keywords: : resveratrol, MnSOD, cervix, p53, resveratrol, hydroxylated resveratrol analogues, cervix cancer, HeLa, C33A, antioxidants, oxidative stress.