title: ortho-Quinone tanshinones directly inhibit telomerase through an oxidative mechanism mediated by hydrogen peroxide.
abstract: The tanshinone natural products possess a variety of pharmacological properties including anti-bacterial, anti-inflammatory, anti-oxidant, and anti-neoplastic activity. The molecular basis of these effects, however, remains largely unknown. In the present study, we explored the direct effect of tanshinones on the enzyme telomerase. Telomerase is up-regulated in the majority of cancer cells and is essential for their survival, making it a potential anti-cancer drug target. We found that the ortho-quinone tanshinone II-A inhibits telomerase in a time- and DTT-dependent fashion, and the hydrogen peroxide scavenger catalase protected telomerase from inactivation. These findings demonstrate that ortho-quinone containing tanshinones can inhibit telomerase owing to their ability to generate reactive oxygen species. The results also provide evidence that telomerase is directly and negatively regulated by reactive oxygen species.
authors: Eshelman School of Pharmacy, Division of Chemical Biology and Medicinal Chemistry, University of North Carolina, Chapel Hill, NC 27599-7568, USA.
authors: Joana
authors: J
authors: Soares
authors: Brian R
authors: BR
authors: Keppler
authors: Xihong
authors: X
authors: Wang
authors: Kuo-Hsiung
authors: KH
authors: Lee
authors: Michael B
authors: MB
authors: Jarstfer
mesh_terms: D045784:Abietanes / Q000737:chemistry* / Q000494:pharmacology; D016227:Benzoquinones / Q000737:chemistry*; D002374:Catalase / Q000378:metabolism; D045744:Cell Line, Tumor; D004229:Dithiothreitol / Q000737:chemistry / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D010084:Oxidation-Reduction; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D045784:Abietanes; D016227:Benzoquinones; D004791:Enzyme Inhibitors; C021751:tanshinone; C004532:quinone; D006861:Hydrogen Peroxide; D002374:Catalase; D019098:Telomerase; D004229:Dithiothreitol