title: Synergistic and cytotoxic action of indole alkaloids produced from elicited cell cultures of Catharanthus roseus.
abstract: BACKGROUND
  Catharanthus roseus (L.) G. Don (Apocynaceae) is a medicinal plant that produces more than 130 alkaloids, with special attention given to the production of the anti-hypertensive monomeric indole alkaloids, serpentine and ajmalicine, and the antitumor dimeric alkaloids, vinblastine and vincristine.
  
  
  OBJECTIVE
  This study evaluated the cytotoxic activity of the indole alkaloid-enriched bioactive extract obtained from suspension cultured-cells of C. roseus elicited with methyl jasmonate (MJ) and cyclodextrins (CDs) in three cell lines: JURKAT E.6 human lymphocytic leukemia, THP-1 human monocytic leukemia and BL 1395 non-tumor human B-cell line.
  
  
  METHODS
  An indole alkaloid-enriched bioactive extract was obtained from C. roseus cell cultures elicited with MJ and CDs. The indole alkaloids were identified using an HPLC-diode array system coupled to a time-of-flight mass spectrometer using electrospray ionization (ESI) source. The cytotoxic assays were made using the colorimetric assay 2, 3-bis (2-methoxy-4-nitro-5-sulfophenyl)-S-[(phenylamino)carbonyl]-2 tetrazolium hydroxide (XTT).
  
  
  RESULTS
  Four indole alkaloids were identified (catharanthine, ajmalicine, tabersonine and lochnericine) but only catharanthine and ajmalicine were quantified. The concentration of the indole alkaloid-enriched bioactive extract that inhibited cell growth by 50% was 211 and 210 ng/mL for the JURKAT E.6 and THP-1 cell lines, respectively.
  
  
  CONCLUSIONS
  The results confirm that the powerful antitumor activity of this indole alkaloid-enriched bioactive extract is not due to the effect of a single compound but depends on the synergistic action of the four compounds identified.
authors.affiliation: Department of Plant Biology, Faculty of Biology, University of Murcia, Campus Universitario de Espinardo, 30100 Murcia, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Fernández-Pérez
authors.forename: Lorena
authors.initials: L
authors.lastname: Almagro
authors.forename: Maria A
authors.initials: MA
authors.lastname: Pedreño
authors.forename: Laura V
authors.initials: LV
authors.lastname: Gómez Ros
mesh_terms: D000085:Acetates / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D030008:Catharanthus / Q000737:chemistry / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D003505:Cyclodextrins / Q000494:pharmacology; D003517:Cyclopentanes / Q000494:pharmacology; D055808:Drug Discovery; D006801:Humans; D026121:Indole Alkaloids / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D054883:Oxylipins / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018515:Plant Leaves / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011804:Quinolines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D046948:Secologanin Tryptamine Alkaloids / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization; D014748:Vinca Alkaloids / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000085:Acetates; D000972:Antineoplastic Agents, Phytogenic; C046419:Catharanthus roseus extract; D003505:Cyclodextrins; D003517:Cyclopentanes; D026121:Indole Alkaloids; D054883:Oxylipins; D010936:Plant Extracts; D011804:Quinolines; D046948:Secologanin Tryptamine Alkaloids; D014748:Vinca Alkaloids; C009373:tabersonine; C005709:raubasine; C072239:methyl jasmonate; C017836:catharanthine; C582596:lochnericine