Abstract Title:

Antiglioma action of xanthones from Gentiana kochiana: Mechanistic and structure-activity requirements.

Abstract Source:

Bioorg Med Chem. 2008 May 15;16(10):5683-94. Epub 2008 Mar 30. PMID: 18406151

Abstract Author(s):

Aleksandra Isakovic, Teodora Jankovic, Ljubica Harhaji, Sladjana Kostic-Rajacic, Zoran Nikolic, Vlatka Vajs, Vladimir Trajkovic

Abstract:

Full Citation: "The present study identifies xanthones gentiakochianin and gentiacaulein as the active principles responsible for the in vitro antiglioma action of ether and methanolic extracts of the plant Gentiana kochiana. Gentiakochianin and gentiacaulein induced cell cycle arrest in G(2)/M and G(0)/G(1) phases, respectively, in both C6 rat glioma and U251 human glioma cell lines. The more efficient antiproliferative action of gentiakochianin was associated with its ability to induce microtubule stabilization in a cell-free assay. Both the xanthones reduced mitochondrial membrane potential and increased the production of reactive oxygen species in glioma cells, but only the effects of gentiakochianin were pronounced enough to cause caspase activation and subsequent apoptotic cell death. The assessment of structure-activity relationship in a series of structurally related xanthones from G. kochiana and Gentianella austriaca revealed dihydroxylation at positions 7, 8 of the xanthonic nucleus as the key structural feature responsible for the ability of gentiakochianin to induce microtubule-associated G(2)/M cell block and apoptotic cell death in glioma cells."

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