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In vitro Antiproliferative Effects of the Indole Alkaloid Vallesiachotamine on Human Melanoma Cells
Paula R. O. Soares,Lidia Andreu Guillo,Pollyana Laurindo de Oliveira,Cecília M. A. de Oliveira,Lucilia Kato 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.3
In course of a screening for small molecules presenting potential anticancer properties, a known monoterpene indole alkaloid named vallesiachotamine was isolated from the leaves of Palicourea rigida (Rubiaceae) collected in the Brazilian Cerrado. The structure was determined by spectroscopic methods, mainly 1D- and 2D-NMR and its biological activities were investigated on cultured human (SK-MEL-37) melanoma cells. In vitro cytotoxicity was evaluated by the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The inhibitory concentration (IC50) was 14.7 ± 1.2 μM for 24 h of drug exposure. Flow cytometry analysis revealed that vallesiachotamine induced G0/G1 arrest and increased the proportion of sub-G1 hypodiploid cells (at 11 μM and 22 μM) and this effect was not dependent on time of incubation. At these concentrations, a typical ladder was observed by agarose gel electrophoresis of the extracted DNA. Treatment of cells with 50 μM vallesiachotamine for 24 h caused extensive cytotoxicity and necrosis. Our results demonstrated that the indole alkaloid vallesiachotamine exhibited important cytotoxicity toward human melanoma cells and that apoptosis and necrosis might be responsible for the observed events.