Klauser, Ellen, Guelden, Michael, Maser, Edmund, Seibert, Sabine and Seibert, Hasso (2014) Additivity, antagonism, and synergy in arsenic trioxide-induced growth inhibition of C6 glioma cells: Effects of genistein, quercetin and buthionine-sulfoximine. Food and Chemical Toxicology, 67 . pp. 212-221.

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Abstract

Arsenic trioxide (ATO) induces clinical remission in acute promyelocytic leukemia and growth inhibition in various cancer cell lines in vitro. Recently, genistein and quercetin were reported to potentiate ATO-provoked apoptosis in leukemia and hepatocellular carcinoma cells. Genistein acted via enhanced ROS generation and quercetin via glutathione depletion. Searching for potential strategies for the treatment of malignant gliomas in this study the capacity of these flavonoids to sensitize rat C6 astroglioma cells for the cytotoxic action of ATO was investigated. ATO inhibited cell growth in a concentration- and time-dependent manner. This effect was accompanied neither by enhanced radical generation nor lipid peroxidation and was not attributed to apoptosis. ATO treatment concentration-dependently increased glutathione levels. Genistein enhanced radical generation. Combined with ATO it inhibited cell growth additively. Additivity was also obtained after cotreatment with ATO and H2O2. Quercetin acted antagonistically on ATO-induced growth inhibition. Quercetin increased glutathione levels. In contrast, buthionine-sulfoximine (BSO) depleted cellular glutathione and acted synergistically with ATO. In conclusion, in C6 cells neither genistein nor quercetin are suited as sensitizing agent, in contrast to BSO. Depletion of cellular glutathione content rather than an increase of ROS generation plays a central role in the enhancement of ATO-toxicity in C6 cells. (C) 2014 Elsevier Ltd. All rights reserved.

Document Type:	Article
Additional Information:	Times Cited: 0 0
Research affiliation:	Kiel University OceanRep > The Future Ocean - Cluster of Excellence
Projects:	Future Ocean
Date Deposited:	30 Mar 2015 12:28
Last Modified:	24 Sep 2019 00:07
URI:	https://oceanrep.geomar.de/id/eprint/27749

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