title: Cytotoxicity of methanol extracts ofAnnona muricata,Passiflora edulisand nine other Cameroonian medicinal plants towards multi-factorial drug-resistant cancer cell lines.
abstract: BACKGROUND
  Cancer cells rapidly acquire resistance leading to treatment failures. In the present study, we have evaluated the cytotoxicity of 17 methanol extracts from 11 Cameroonian medicinal plants against the sensitive leukemia CCRF-CEM cells and the best ones were further tested on a panel of 8 other human cancer cell lines, including various MDR phenotypes as well as against the normal AML12 hepatocytes.
  
  
  METHODS
  The cytotoxicity of the extracts was determined using a resazurin reduction assay meanwhile flow cytometry was used to measure cell cycle, apoptosis, mitochondrial membrane potential (MMP), and reactive oxygen species.
  
  
  RESULTS
  In an initial screening using leukemia CCRF-CEM cells, ten extracts from five plants namelyAlchornea floribunda,Annona muricata,Euphorbia prostata,Pachypodanthium staudtiiandPassiflora edulisdisplayed IC50values below 20 µg/mL. They were further tested in 8 other cell lines as well as in normal AML12 hepatocytes. All selected extracts were active against leukemia CEM/ADR5000 cells with IC50value below 40 µg/mL. IC50values ranging from 10.13 µg/mL (towards CEM/ADR5000 cells) to 72.01 µg/mL [towards resistant colon carcinoma HCT116 (p53-/-) cells] forPachypodanthium staudtiiroots and from 0.11 µg/mL (towards CCRF-CEM cells) to 108 µg/mL (towards P-glycoprotein-over-expressing CEM/ADR5000 cells) for doxorubicin were obtained in the eight other cancer cell lines studied. Extracts fromAnnona muricataleaves (AML) and seeds (AMS), andPassiflora edulisfruit (PEF) had IC50values below 1 µg/mL against CCRF-CEM cells and below 10 µg/mL against its MDR subline CEM/ADR5000 cells. AML, AMS and PEF induced MMP-loss-mediated apoptosis in CCRF-CEM cells.
  
  
  CONCLUSIONS
  Results of the present study suggest that some of the tested plants namelyAlchornea floribunda,Annona muricata,Euphorbia prostata,Pachypodanthium staudtiiandPassiflora edulisrepresent a source of anticancer drugs.Annona muricataandPassiflora edulisare good cytotoxic plants that could be exploited to develop phytomedicine to fight mostly hematological cancers including MDR phenotypes.
authors.affiliation: Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, University of Mainz, 55128 Mainz, Germany ; Department of Biochemistry, Faculty of Science, University of Dschang, P.O. Box 67, Dschang, Cameroon.
authors.forename: Victor
authors.initials: V
authors.lastname: Kuete
authors.affiliation: Department of Biochemistry, Faculty of Science, University of Dschang, P.O. Box 67, Dschang, Cameroon.
authors.forename: Joachim K
authors.initials: JK
authors.lastname: Dzotam
authors.affiliation: Department of Biochemistry, Faculty of Science, University of Dschang, P.O. Box 67, Dschang, Cameroon.
authors.forename: Igor K
authors.initials: IK
authors.lastname: Voukeng
authors.affiliation: Department of Biochemistry, Faculty of Science, University of Dschang, P.O. Box 67, Dschang, Cameroon.
authors.forename: Aimé G
authors.initials: AG
authors.lastname: Fankam
authors.affiliation: Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, University of Mainz, 55128 Mainz, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Efferth
keywords: Annona muricata; Apoptosis; Cameroon; Cytotoxicity; Medicinal plants; Passiflora edulis