title: Euphorbia Species-derived Diterpenes and Coumarins as Multidrug Resistance Modulators in Human Colon Carcinoma Cells.
abstract: BACKGROUND
  Recently, many new potent multidrug resistance (MDR) reversal agents have been discovered, among them lathyrane and jatrophane diterpenes isolated from various Euphorbia species. In the present study, the cytotoxicity, P-glycoprotein inhibition activity, and MDR reversal potency of six diterpenes and two coumarins from two Euphorbia species were studied in human colon carcinoma LoVo cells, and doxorubicin-resistant, LoVo/Dx cells.
  
  
  METHODS
  Cytotoxicity of the studied compounds (alone and in combination with doxorubicin) was investigated. Inhibition of P-glycoprotein transport activity was monitored by flow cytometry. Changes in intracellular doxorubicin accumulation were observed by means of fluorescence microscopy.
  
  
  RESULTS
  Latilagascene B was demonstrated to be an effective P-glycoprotein inhibitor, able to increase doxorubicin accumulation in resistant cells, however not able to restore doxorubicin cytotoxicity in LoVo/Dx cells.
  
  
  CONCLUSIONS
  The structure of latilagascene B seems to be an interesting candidate for further synthesis of new derivatives of reduced cytotoxicity and high anti-MDR potency.
authors.affiliation: Department of Biophysics, Wrocław Medical University, Wrocław, Poland Department of Biochemistry, Wrocław Medical University, Wrocław, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Wiśniewski
authors.affiliation: Department of Biophysics, Wrocław Medical University, Wrocław, Poland olga.wesolowska@umed.wroc.pl.
authors.forename: Olga
authors.initials: O
authors.lastname: Wesołowska
authors.affiliation: Department of Biophysics, Wrocław Medical University, Wrocław, Poland.
authors.forename: Kamila
authors.initials: K
authors.lastname: Środa-Pomianek
authors.affiliation: Laboratory of Glycobiology and Cellular Interactions, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Paprocka
authors.affiliation: Laboratory of Glycobiology and Cellular Interactions, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Bielawska-Pohl
authors.affiliation: Laboratory of Glycobiology and Cellular Interactions, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Krawczenko
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Noelia
authors.initials: N
authors.lastname: Duarte
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Maria-José U
authors.initials: MJ
authors.lastname: Ferreira
authors.affiliation: Laboratory of Glycobiology and Cellular Interactions, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.
authors.forename: Danuta
authors.initials: D
authors.lastname: Duś
authors.affiliation: Department of Biophysics, Wrocław Medical University, Wrocław, Poland.
authors.forename: Krystyna
authors.initials: K
authors.lastname: Michalak
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000037:antagonists & inhibitors; D000230:Adenocarcinoma / Q000473:pathology*; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D045744:Cell Line, Tumor; D002934:Cinnamates / Q000302:isolation & purification / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000473:pathology*; D003374:Coumarins / Q000302:isolation & purification / Q000494:pharmacology*; D004224:Diterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D004317:Doxorubicin / Q000378:metabolism; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D028481:Euphorbia / Q000737:chemistry*; D005456:Fluorescent Dyes / Q000378:metabolism; D006801:Humans; D015394:Molecular Structure; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors; D010936:Plant Extracts / Q000737:chemistry
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000972:Antineoplastic Agents, Phytogenic; D002934:Cinnamates; D003374:Coumarins; D004224:Diterpenes; D005456:Fluorescent Dyes; D009363:Neoplasm Proteins; D010936:Plant Extracts; C000613765:latilagascene B; D004317:Doxorubicin
keywords: Diterpenes; Euphorbia; P-glycoprotein; coumarins; multidrug resistance (MDR)