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. 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 chain reaction

Research of steroidal compounds as anticancer agents started almost 50 years ago. During the past decades, several innovative new steroids, like cyproterone, finasteride, estramustin, exemestane and fulvestrant have successfully become a part of routine clinical practice. Meanwhile, a vast amount of new information have accumulated about the functions of the endogenous steroid system (including the characterization of enzymes, receptors, transcription pathways, etc.) and about the role of steroids in carcinogenesis. Therefore, it is regularly required to review the latest published results, focusing on a well-defined part within this research field that has definitely developed into a highly diversified speciality by now. Herein, we make an attempt to summarize the most recent results reported about anticancer agents of estrane backbone, focusing on their mechanisms of action and their structure-activity relationships. Due to the vast number and various accessibilities of scientific publications, neither other reviews nor this one can be considered as absolutely exhaustive. In spite of these restrictive factors, the current review makes a good opportunity to define the recent scientific trends in the field of estradiol-related anticancer agents.