title: Cytotoxicity and apoptosis induced by alfalfa (Medicago sativa) leaf extracts in sensitive and multidrug-resistant tumor cells.
abstract: Alfalfa (Medicago sativa) has been used to cure a wide variety of ailments. However, only a few studies have reported its anticancer effects. In this study, extracts were obtained from alfalfa leaves and their cytotoxic effects were assessed on several sensitive and multidrug-resistant tumor cells lines. Using the mouse leukaemia P388 cell line and its doxorubicin-resistant counterpart (P388/DOX), we showed that the inhibition of cell growth induced by alfalfa leaf extracts was mediated through the induction of apoptosis, as evidenced by DNA fragmentation analysis. The execution of programmed cell death was achieved via the activation of caspase-3, leading to PARP cleavage. Fractionation of toluene extract (To-1), the most active extract obtained from crude extract, led to the identification of 3 terpene derivatives and 5 flavonoids. Among them, (-)-medicarpin, (-)-melilotocarpan E, millepurpan, tricin, and chrysoeriol showed cytotoxic effects in P388 as well as P388/DOX cells. These results demonstrate that alfalfa leaf extract may have interesting potential in cancer chemoprevention and therapy.
authors.affiliation: a Laboratoire de Biochimie et Biologie Moléculaire , Faculté de Pharmacie, URCA , Reims , France.
authors.forename: Grégory
authors.initials: G
authors.lastname: Gatouillat
authors.forename: Abdulmagid Alabdul
authors.initials: AA
authors.lastname: Magid
authors.forename: Eric
authors.initials: E
authors.lastname: Bertin
authors.forename: Marie-Genevieve
authors.initials: MG
authors.lastname: Okiemy-Akeli
authors.forename: Hamid
authors.initials: H
authors.lastname: Morjani
authors.forename: Catherine
authors.initials: C
authors.lastname: Lavaud
authors.forename: Claudie
authors.initials: C
authors.lastname: Madoulet
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D007941:Leukemia P388 / Q000188:drug therapy* / Q000473:pathology; D000455:Medicago sativa / Q000737:chemistry*; D051379:Mice; D010936:Plant Extracts / Q000032:analysis / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D004317:Doxorubicin; D053148:Caspase 3