Investigation of Cytotoxic Activity on Human Cancer Cell Lines of Arborinine and Furanoacridones Isolated from Ruta graveolens

作者：Borbála Réthy, István Zupkó, Renáta Minorics, Judit Hohmann, Imre Ocsovszki, George Falkay · 发表于：Planta Medica · 年份：2006 · DOI：10.1055/s-2006-951747 · 被引用次数：49 · 研究领域：Plant chemical constituents analysis、Synthesis and Biological Activity、Phytochemical compounds biological activities

The cytotoxic effects of a series of furanoacridones isolated from Ruta graveolens L. (Rutaceae) and of two further acridone alkaloids (arborinine and evoxanthine) were investigated by means of the MTT assay, using the human cell lines HeLa, MCF7 and A431. Arborinine proved best in inhibiting the proliferation of all three cell lines. The cytotoxic potency of the furacridone alkaloids was a function of their lipid solubility, which was determined by means of PAMPA. The capacity of the most effective furanoacridones to induce apoptosis was demonstrated by flow cytometric cell cycle analysis and by staining with ethidium bromide and acridine orange. This finding was reinforced by determining the apoptosis-regulating factors Bcl-2 and Bax, which were revealed by means of RT-PCR to change dose-dependently. The data presented here indicate that naturally occurring furanoacridones can be regarded as excellent starting structures for the potential development of new anticancer agents. Abbreviations AO:acridine orange cDNA:copy deoxyribonucleic acid DMSO:dimethyl sulfoxide dNTP:deoxyribonucleotide triphosphate EB:ethidium bromide hGAPDH:human glyceraldehyde-3-phosphate dehydrogenase MMLV-RT:moloney murine leukemia virus-reverse transcriptase mRNA:messenger ribonucleic acid MTT:3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide PAMPA:parallel artificial membrane permeability assays PBS:phosphate buffered saline RNA:ribonucleic acid RT-PCR:reverse transcription-polymerase cha...