Abstract #2658: Trisindoline and indirubin-3\#8217;-monoxime exert anticancer activity through different mechanism.

Abstract

Recently, novel indigoid metabolites produced from Rhodococcus-derived oxygenase with anti-cancer activity were reported and active compound trisindoline was isolated (Biochem Biophys Res Commun, 376: 96). Trisindoline showed cytotoxicity against colorectal carcinoma HCT15 cells and uterine sarcoma MES-SA cells. Here, in an effort to find the mechanism of trisinoline\#8217;s cytotoxic activity, we compared trisindoline with indirubin-3\#8217;-monoxime, a bis-indole indigoid compound. Indirubin-3-\#8217;monoxime is mainly recognized as an inhibitor of cyclin-dependent kinase and glycogen synthase kinase-3, and has been considered for anticancer agent. In this report, we compared the cytotoxic activity of trisindoline and indirubin-3\#8217;-monoxime and studied the mechanism of action. Whereas trisindoline and indirubin-3\#8217;-monoxime showed similar activity against cancer cells, they exhibited different mode of action. Indirubin-3\#8217;-monoxime inhibited kinases like Flt-3, VEGFR2, and Met, which are major oncology target in drug discovery. IC₅₀ of Indirubin-3\#8217;-monoxime was 0.142 \#956;M for Flt-3, 1.48 \#956;M for VEGFR2, and 5.5 \#956;M for Met. However, trisindoline do not affect the activities of these kinases. Although trisindoline and indirubin-3\#8217;-monoxime both belong to indigoid compound and exhibit similar cytotoxic activity, they have different mode of action for their anti-cancer activity.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2658.