title: Antioxidant and selective anticancer activities of two Euphorbia species in human acute myeloid leukemia.
abstract: In this study, two Euphorbia species (i.e. terracina and paralias) were investigated for their cytotoxic and antioxidant activities. Cytotoxicity of plant methanol and chloroform fractions was examined towards human acute myeloid leukemia (THP1) and human colon epithelial (Caco2) cancer cell lines, as well as CD 14 and IEC-6 normal cells by targeting various modulators of apoptosis or inflammation. Moreover, secondary metabolite pools (phenolic classes, alkaloids, terpenes, saponins) and antioxidant activities (DPPH, ABTS and O2- scavenging, as well as FRAP tests) were assessed in plant extracts. Both Euphorbia species appeared to be rich in phenolic compounds and terpenoids, Moreover, E. terracina polar and apolar fractions and E. paralias polar fraction were highly active against THP1 cells, with IC50values of 2.08, 14.43 and 54.58μg/mL, respectively. However, no cytotoxicity was found against normal cells (CD14+monocytes). The results indicate that the three fractions induce apoptosis in THP1 cell line after 6h of exposure. Furthermore, apoptosis caused by apolar fraction was related to a caspase-dependent process, whereas other death pathways seemed to be involved with the polar fractions. An enhanced production of reactive oxygen species was detected upon cell treatment with plant extracts. Interestingly, they have no effect on cytokine TNF-α secretion in THP1 and normal cells compared to untreated cells, indicating that the three fractions caused no inflammation. Euphorbia terracina and E. paralias polar fractions showed strong antioxidant activity with potent scavenging capacity against DPPH, ABTS and superoxide radicals. Moreover, these fractions displayed a very high ferric reducing power. These findings confirm the strong antioxidant capacity of Euphorbia plants and suggest a targeted anti-cancer effect with a potent anti-proliferative property of E. terracina and E. paralias extracts, which induce programmed cell death in leukemia cell lines but not in normal monocytes cells.
authors.affiliation: Laboratoire des Plantes Aromatiques et Médicinales, Centre de Biotechnologie de Borj-Cédria (CBBC), BP 901, 2050 Hammam-Lif, Tunisie; Université de Tunis El Manar, Unité de Physiologie et Biochimie de la Réponse des Plantes aux Contraintes Abiotiques, Département de Biologie, 1068 Tunis, Tunisie. Electronic address: Soumaya.BJannet.Lachaal@gmail.com.
authors.forename: Soumaya
authors.initials: S
authors.lastname: Ben Jannet
authors.affiliation: Laboratoire de Biodiversité et d'Écologie Microbienne (EA 3882), Université de Brest, Parvis Blaise Pascal, 29280 Plouzané, France.
authors.forename: Nolwenn
authors.initials: N
authors.lastname: Hymery
authors.affiliation: Laboratoire des Plantes Aromatiques et Médicinales, Centre de Biotechnologie de Borj-Cédria (CBBC), BP 901, 2050 Hammam-Lif, Tunisie.
authors.forename: Soumaya
authors.initials: S
authors.lastname: Bourgou
authors.affiliation: Laboratoire des Plantes Aromatiques et Médicinales, Centre de Biotechnologie de Borj-Cédria (CBBC), BP 901, 2050 Hammam-Lif, Tunisie; Laboratoire de Géoarchitecture (EA 2219), Université de Brest, 6 avenue V. Le Gorgeu, CS 93837, Brest Cedex 3, France.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Jdey
authors.affiliation: Université de Tunis El Manar, Unité de Physiologie et Biochimie de la Réponse des Plantes aux Contraintes Abiotiques, Département de Biologie, 1068 Tunis, Tunisie.
authors.forename: Mokhtar
authors.initials: M
authors.lastname: Lachaal
authors.affiliation: Laboratoire de Géoarchitecture (EA 2219), Université de Brest, 6 avenue V. Le Gorgeu, CS 93837, Brest Cedex 3, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Magné
authors.affiliation: Laboratoire des Plantes Aromatiques et Médicinales, Centre de Biotechnologie de Borj-Cédria (CBBC), BP 901, 2050 Hammam-Lif, Tunisie.
authors.forename: Riadh
authors.initials: R
authors.lastname: Ksouri
mesh_terms: D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D018938:Caco-2 Cells; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D028481:Euphorbia / Q000737:chemistry*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology; D013729:Terpenes / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000470:Alkaloids; D000970:Antineoplastic Agents; D000975:Antioxidants; D010636:Phenols; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D012503:Saponins; D013729:Terpenes; D014409:Tumor Necrosis Factor-alpha
keywords: Antioxidants; Apoptosis; E. paralias; E. terracina; In vitro cytotoxicity; Inflammatory; Leukemia