title: Cytotoxicity and inhibition of P-glycoprotein by selected medicinal plants from Thailand.
abstract: BACKGROUND
  Thai medicine has a long tradition of tonifying medicinal plants. In the present investigation, we studied the flower extracts of Jasminum sambac, Mammea siamensis, Mesua ferrea, Michelia alba, Mimusops elengi, and Nelumbo nucifera and speculated that these plants might influence metabolism and substance flow in the body.
  
  
  METHODS
  Isolation of porcine brain capillary endothelial cells (PBCECs) as well as multidrug-resistance CEM/ADR5000 leukemia cells, MDA-M;B-231 breast cancer, U-251 brain tumor, and HCT-116 colon cancer cells were used. The calcein-acetoxymethylester (AM) assay was used to measure inhibition of P-glycoprotein transport. XTT and resazurin assays served for measuring cytotoxicity.
  
  
  RESULTS
  The extracts revealed cytotoxicity towards CCRF-CEM leukemia cells to a different extent. The strongest growth inhibition was found for the n-hexane extracts of Mammea siamensis and Mesua ferrea, and the dichloromethane extracts of Mesua ferrea and Michelia alba. The flower extracts also inhibited P-glycoprotein function in porcine brain capillary endothelial cells and CEM/ADR5000 leukemia cells, indicating modulation of the blood-brain barrier and multidrug resistance of tumors. Bioactivity-guided isolation of coumarins from Mammea siamensis flowers revealed considerable cytotoxicity of mammea A/AA, deacetylmammea E/BA and deacetylmammea E/BB towards human MDA-MB-231 breast cancer, U-251 brain tumor, HCT-116 colon cancer, and CCRF-CEM leukemia cells.
  
  
  CONCLUSIONS
  The plants analyzed may be valuable in developing novel treatment strategies to overcome the blood-brain barrier and multidrug-resistance in tumor cells mediated by P-glycoprotein.
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Pharmacognosy, Karl-Franzens-University Graz, Graz, Austria; Department of Pharmacognosy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand; Thai Traditional Medicine College, Rajamangala University of Technology Thayaburi, Phathumthani, Thailand.
authors.forename: Chanai
authors.initials: C
authors.lastname: Noysang
authors.affiliation: Institute of Pharmacy and Molecular Biotechnology, Department of Pharmaceutical Technology and Pharmacology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Mahringer
authors.affiliation: Institute of Pharmacy and Biochemistry, Department of Pharmaceutical Biology, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany.
authors.forename: Maen
authors.initials: M
authors.lastname: Zeino
authors.affiliation: Institute of Pharmacy and Biochemistry, Department of Pharmaceutical Biology, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Saeed
authors.affiliation: Department of Pharmacognosy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.
authors.forename: Omboon
authors.initials: O
authors.lastname: Luanratana
authors.affiliation: Institute of Pharmacy and Molecular Biotechnology, Department of Pharmaceutical Technology and Pharmacology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Gert
authors.initials: G
authors.lastname: Fricker
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Pharmacognosy, Karl-Franzens-University Graz, Graz, Austria.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Bauer
authors.affiliation: Institute of Pharmacy and Biochemistry, Department of Pharmaceutical Biology, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany. Electronic address: efferth@uni-mainz.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Efferth
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000098:blood supply / Q000187:drug effects; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D035264:Flowers; D006801:Humans; D008518:Medicine, East Asian Traditional; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry*; D013552:Swine; D013785:Thailand
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts
keywords: ABC transporter; Blood–brain barrier; Chemotherapy; Herbal therapy; Multidrug resistance; Natural products