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Molecules 2014, 19(12), 20054-20072; doi:10.3390/molecules191220054

Resveratrol Modulates the Topoisomerase Inhibitory Potential of Doxorubicin in Human Colon Carcinoma Cells

Department of Food Chemistry and Toxicology, University of Vienna, Währinger Str. 38, 1090 Wien, Austria
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Received: 3 September 2014 / Revised: 24 November 2014 / Accepted: 25 November 2014 / Published: 1 December 2014
(This article belongs to the Special Issue Resveratrol)
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Abstract

Resveratrol (RSV) is currently being widely discussed as potentially useful for anticancer therapy in combination with classical chemotherapeutics, e.g., the topoisomerase II (TOP II) poison doxorubicin (DOX). However, there is still a lack of knowledge of possible interference at the target enzyme, especially since RSV itself has recently been described to act as a TOP poison. We therefore sought to address the question whether RSV affects DOX-induced genotoxic and cytotoxic effects with special emphasis on TOP II in HT-29 colon carcinoma cells. RSV was found to counteract DOX-induced formation of DNA-TOP-intermediates at ≥100 µM for TOP IIα and at 250 µM for TOP IIβ. As a consequence, RSV modulated the DNA-strand breaking potential of DOX by mediating protective effects with an apparent maximum at 100 µM. At higher concentration ranges (≥200 µM) RSV diminished the intracellular concentrations of DOX. Nevertheless, the presence of RSV slightly enhanced the cytotoxic effects of DOX after 1.5 h and 24 h of incubation. Taken together, at least in cell culture RSV was found to affect the TOP-poisoning potential of DOX and to modulate its cytotoxic effectiveness. Thus, further studies are needed to clarify the impact of RSV on the therapeutic effectiveness of DOX under in vivo conditions. View Full-Text
Keywords: resveratrol; doxorubicin; colon cancer; topoisomerase resveratrol; doxorubicin; colon cancer; topoisomerase
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Schroeter, A.; Marko, D. Resveratrol Modulates the Topoisomerase Inhibitory Potential of Doxorubicin in Human Colon Carcinoma Cells. Molecules 2014, 19, 20054-20072.

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