title: Ligaria cuneifolia flavonoid fractions modulate cell growth of normal lymphocytes and tumor cells as well as multidrug resistant cells.
abstract: Flavonoids are ubiquitous compounds present in plant extracts. They represent a major active component of the plant extract and are often known for their anti-inflammatory and anti-tumor effects. Previously, we demonstrated that Ligaria cuneifolia (R et P) Tiegh. (Loranthaceae) extracts inhibit proliferation of murine mitogen-activated lymphocytes as well as murine T leukaemia (LB) and breast tumor cells (MMT). The aim of this study was to assess the anti-proliferative and pro-apoptotic activities of three separate flavonoid fractions derived from L. cuneifolia whole extract (aqueous, methanolic and ethyl acetate) on normal and tumor cells. This was performed as a bio-guided approach leading to the isolation and identification of the active compounds responsible for the effects observed with the whole extract. Results showed that the three fractions differed in the amount and type of compounds found. Only the ethyl acetate flavonoid fraction (100 microg/ml) was able to inhibit significantly the proliferation of Con A stimulated splenocytes or LB and MMT cells. Inhibition of proliferation was mediated by apoptosis as determined by morphology and DNA hypodiploidy. The ethyl acetate fraction modified mRNA expression of IL-2, IL-10 and TGF-beta, while the methanol fraction only modified IL-10 mRNA on LB cells. Our results show that the ethyl acetate flavonoid fraction contains the most active compound/s and is the potential candidate to isolate the active compound/s responsible for the effects observed with L. cuneifolia whole extract.
authors.affiliation: Cátedra de Inmunología, Instituto de Estudios de la Inmunidad Humoral - Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, República Argentina.
authors.forename: Paula
authors.initials: P
authors.lastname: Cerdá Zolezzi
authors.forename: Teresa
authors.initials: T
authors.lastname: Fernández
authors.forename: Paula
authors.initials: P
authors.lastname: Aulicino
authors.forename: Victoria
authors.initials: V
authors.lastname: Cavaliere
authors.forename: Sofía
authors.initials: S
authors.lastname: Greczanik
authors.forename: Eloisi
authors.initials: E
authors.lastname: Caldas Lopes
authors.forename: Marcelo
authors.initials: M
authors.lastname: Wagner
authors.forename: Rafael
authors.initials: R
authors.lastname: Ricco
authors.forename: Alberto
authors.initials: A
authors.lastname: Gurni
authors.forename: Silvia
authors.initials: S
authors.lastname: Hajos
authors.forename: Elida
authors.initials: E
authors.lastname: Alvarez
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape; D002478:Cells, Cultured; D005591:Chemical Fractionation; D016207:Cytokines / Q000235:genetics; D004247:DNA / Q000235:genetics; D004171:Diploidy; D018432:Drug Resistance, Multiple; D005260:Female; D005419:Flavonoids / Q000302:isolation & purification* / Q000494:pharmacology*; D028183:Loranthaceae / Q000737:chemistry*; D008214:Lymphocytes / Q000166:cytology* / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000187:drug effects
chemical_list: D016207:Cytokines; D005419:Flavonoids; D012333:RNA, Messenger; D004247:DNA