title: Cytotoxic effect of Reseda lutea L.: A case of forgotten remedy.
abstract: BACKGROUND
  Reseda lutea L. (Resedaceae) or Wild Mignonette is a widely distributed plant species. Pliny the Elder (AD 23-AD 79), a Roman scholar and naturalist, reported the use of R. lutea for reducing tumors in his Historia naturalis. Accounts of the beneficial effects of R. lutea in tumor treatment could also be found in the works of later authors, such as Étienne François Geoffroy (1672-1731) and Samuel Frederick Gray (1766-1828). However, to date no in vivo or in vitro evidence exists in support of the alleged tumor healing properties of R. lutea.
  
  
  METHODS
  The composition of autolysates obtained from different organs (root, flower and fruit) of R. lutea was investigated by GC and GC-MS analyses and IR, 1D and 2D NMR spectroscopy. These analyses led to the discovery of a new compound isolated in pure form from the flower autolysate. Autolysates and their major constituents were submitted to MTT-dye reduction cytotoxic assay on human A375 (melanoma) and MRC5 (fibroblast) cell lines. Mechanism of the cytotoxic effects was studied by cell cycle analysis and Annexin V assay.
  
  
  RESULTS
  Benzyl isothiocyanate and 2-(α-l-rhamnopyranosyloxy)benzyl isothiocyanate were identified as the major constituents of the root and flower autolysates, respectively (the later represents a new natural product). These compounds showed significant antiproliferative effects against both cell lines, which could also explain the observed high cytotoxic activity of the tested autolysates. Cell cycle analysis revealed apoptosis as the probable mechanism of cell death.
  
  
  CONCLUSIONS
  Tumor healing properties attributed to R. lutea in the pre-modern texts were substantiated by the herein obtained results. Two isothiocyanates were found to be the major carriers of the observed activity. Although there was a relatively low differential effect of the plant metabolites on transformed and non-transformed cell lines, one can argue that the noted strong cytotoxicity provides first evidence that could explain the long forgotten use of this particular species.
authors: Department of Chemistry, Faculty of Science and Mathematics, University of Niš, Višegradska 33, RS-18000 Niš, Serbia. Electronic address: nikoradulovic@yahoo.com.
authors: Niko S
authors: NS
authors: Radulović
authors: Department of Chemistry, Faculty of Science and Mathematics, University of Niš, Višegradska 33, RS-18000 Niš, Serbia.
authors: Dragan B
authors: DB
authors: Zlatković
authors: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, PO Box 23, RS-11010 Belgrade, Serbia.
authors: Tatjana
authors: T
authors: Ilić-Tomić
authors: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, PO Box 23, RS-11010 Belgrade, Serbia.
authors: Lidija
authors: L
authors: Senerović
authors: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, PO Box 23, RS-11010 Belgrade, Serbia.
authors: Jasmina
authors: J
authors: Nikodinovic-Runic
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D045744:Cell Line, Tumor; D020834:Ethnopharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D017879:Isothiocyanates / Q000302:isolation & purification / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D010936:Plant Extracts / Q000494:pharmacology*; D031951:Resedaceae / Q000737:chemistry*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017879:Isothiocyanates; D010936:Plant Extracts
keywords: Apoptosis; Cytotoxic effect; Isothiocyanates; Reseda lutea L.; Structure elucidation