Investigation of cytotoxic activity on human cancer cell lines of arborinine and furanoacridones isolated from Ruta graveolens.
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.
Réthy
Borbála
B
Department of Pharmacodynamics and Biopharmacy, University of Szeged, Szeged, Hungary.
Zupkó
István
I
Minorics
Renáta
R
Hohmann
Judit
J
Ocsovszki
Imre
I
Falkay
George
G
D000166:Acridines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D054831:Acridones; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D020128:Inhibitory Concentration 50; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D032105:Ruta; D012995:Solubility; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
D000166:Acridines; D054831:Acridones; D000972:Antineoplastic Agents, Phytogenic; C494826:BAX protein, human; D010936:Plant Extracts; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; C022784:arborinine; C041300:acridone