title: Inhibition of lymphocyte proliferation by prenylated flavones: artelastin as a potent inhibitor.
abstract: Eight natural prenylated flavones, previously isolated from Artocarpus elasticus, were evaluated for their effect on the mitogenic response of human lymphocytes to PHA. They all exhibited a dose-dependent suppression effect. An interesting relationship was observed between their antiproliferative activity and their chemical structure. Indeed, the most potent flavones possessed a 3,3-dymethylallyl group (prenyl) at C-8, such as artelastin, which exhibited the highest antiproliferative activity. Studies of the mechanism underlying its effect revealed that artelastin had an irreversible inhibitory effect on the PHA-induced lymphocyte proliferation and could affect the course of the ongoing mitogenic response either at the initial induction phase or at the late phase of proliferation. This prenylated flavone was also shown to be a potent inhibitor of both T- and B-lymphocyte mitogen induced proliferation although B-mitogenic response was the more sensitive one. Artelastin did not affect either the basal levels of the early marker of activation CD69 on non-stimulated splenocytes or its expression on ConA- or LPS-stimulated splenocytes. However, it decreased the production of IFN-gamma, IL-2, IL-4 and IL-10 in ConA-stimulated splenocytes. Furthermore, artelastin had no effect on apoptosis of splenocytes.
authors.affiliation: Centro de Estudos de Química Orgânica, Fitoquímica e Farmacologia da Universidade do Porto, Porto, Portugal.
authors.forename: F
authors.initials: F
authors.lastname: Cerqueira
authors.forename: A
authors.initials: A
authors.lastname: Cordeiro-da-Silva
authors.forename: N
authors.initials: N
authors.lastname: Araújo
authors.forename: H
authors.initials: H
authors.lastname: Cidade
authors.forename: A
authors.initials: A
authors.lastname: Kijjoa
authors.forename: M S J
authors.initials: MS
authors.lastname: Nascimento
mesh_terms: D000818:Animals; D031622:Artocarpus / Q000737:chemistry; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D010835:Phytohemagglutinins / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018547:Plant Stems / Q000737:chemistry; D017368:Protein Prenylation; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism
chemical_list: D005419:Flavonoids; D010835:Phytohemagglutinins; D010936:Plant Extracts; C477276:artelastin