title: Cytotoxicity of two naturally occurring flavonoids (dorsmanin F and poinsettifolin B) towards multi-factorial drug-resistant cancer cells.
abstract: BACKGROUND
  The expression of diverse resistance mechanisms in cancer cells is one of the major barriers to successful cancer chemotherapy.
  
  
  METHODS
  In the present study, we assessed the cytotoxicity of two naturally occurring flavonoids dorsmanin F (1, a flavanone) and poinsettifolin B (2, a chalcone) against 9 drug-sensitive and multidrug-resistant (MDR) cancer cell lines. The resazurin reduction assay was used to evaluate the cytotoxicity of these compounds, whilst caspase-Glo assay was used to detect caspase activation. Cell cycle, mitochondrial membrane potential (MMP) and levels of reactive oxygen species (ROS) were all analysed via flow cytometry.
  
  
  RESULTS
  Compounds 1 and 2 displayed cytotoxic effects with IC50 values below 34 µM in all the 9 tested cancer cell lines. The IC50 values for flavanone 1 and chalcone 2 ranged from 5.34 µM and 1.94 µM (towards leukaemia CCRF-CEM cells) to 33.30 µM and 28.92 µM (towards MDA-MB-231-BCRP cells), respectively, and from 0.20 µM (against CCRF-CEM cells) to 195.12 µM (against CEM/ADR5000 cells) for doxorubicin. The compounds induced apoptosis in CCRF-CEM leukaemia cells, mediated by MMP disruption and increased ROS production.
  
  
  CONCLUSIONS
  Dorsmain F and poinsettifolin B are potential cytotoxic natural products that deserve more investigations to develop novel antineoplastic drugs against multifactorial drug-resistant cancers.
authors.affiliation: Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, University of Mainz, Staudinger Weg 5, 55128 Mainz, Germany ; Department of Biochemistry, Faculty of Science, University of Dschang, Dschang, Cameroon.
authors.forename: Victor
authors.initials: V
authors.lastname: Kuete
authors.affiliation: Department of Biochemistry, Faculty of Science, University of Dschang, Dschang, Cameroon.
authors.forename: Armelle T
authors.initials: AT
authors.lastname: Mbaveng
authors.affiliation: Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, University of Mainz, Staudinger Weg 5, 55128 Mainz, Germany.
authors.forename: Maen
authors.initials: M
authors.lastname: Zeino
authors.affiliation: Department of Pharmacognosy and Pharmaceutical Chemistry, Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon.
authors.forename: Bathelemy
authors.initials: B
authors.lastname: Ngameni
authors.affiliation: Department of Chemistry, Higher Teachers' Training College, University of Yaoundé I, Yaoundé, Cameroon.
authors.forename: Gilbert Deccaux W F
authors.initials: GD
authors.lastname: Kapche
authors.affiliation: Department of Chemistry, Higher Teachers' Training College, University of Yaoundé I, Yaoundé, Cameroon.
authors.forename: Simeon F
authors.initials: SF
authors.lastname: Kouam
authors.affiliation: Department of Organic Chemistry, Faculty of Science, University of Yaoundé I, Yaoundé, Cameroon.
authors.forename: Bonaventure T
authors.initials: BT
authors.lastname: Ngadjui
authors.affiliation: Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, University of Mainz, Staudinger Weg 5, 55128 Mainz, Germany . Electronic address: efferth@uni-mainz.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Efferth
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D047188:Chalcones / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D015394:Molecular Structure; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D047188:Chalcones; D005419:Flavonoids; D017382:Reactive Oxygen Species; C478609:dorsmanin F; C000601575:poinsettifolin B; D020169:Caspases
keywords: Apoptosis; Cytotoxicity; Dorsmanin F; Flavonoids; Multi-drug resistance; Poinsettifolin B