title: Antiproliferative activity of pristimerin isolated from Maytenus ilicifolia (Celastraceae) in human HL-60 cells.
abstract: Pristimerin has been shown to be cytotoxic to several cancer cell lines. In the present work, the cytotoxicity of pristimerin was evaluated in human tumor cell lines and in human peripheral blood mononuclear cells (PBMC). This work also examined the effects of pristimerin (0.4; 0.8 and 1.7 microM) in HL-60 cells, after 6, 12 and 24h of exposure. Pristimerin reduced the number of viable cells and increased number of non-viable cells in a concentration-dependent manner by tripan blue test showing morphological changes consistent with apoptosis. Nevertheless, pristimerin was not selective to cancer cells, since it inhibited PBMC proliferation with an IC50 of 0.88 microM. DNA synthesis inhibition assessed by 5-bromo-2'-deoxyuridine (BrdU) incorporation in HL-60 cells was 70% and 83% for the concentrations of 0.4 and 0.8 microM, respectively. Pristimerin (10 and 20 microM) was not able to inhibit topoisomerase I. In AO/EB (acridine orange/ethidium bromide) staining, all tested concentrations reduced the number of HL-60 viable cells, with the occurrence of necrosis and apoptosis in a concentration-dependent manner, results in agreement with trypan blue exclusion findings. The analysis of membrane integrity and internucleosomal DNA fragmentation by flow cytometry in the presence of pristimerin indicated that treated cells underwent apoptosis. The present data point to the importance of pristimerin as representative of an emerging class of potential anticancer chemicals, exhibiting an antiproliferative effect by inhibiting DNA synthesis and triggering apoptosis.
authors.affiliation: Departamento de Fisiologia e Farmacologia, Campus do Porangabussu, UFC, Rua Coronel Nunes de Melo, 1127 - Rodolfo Teófilo, Universidade Federal do Ceará, Caixa Postal 3157, 60430-270 Fortaleza, Ceará, Brazil.
authors.forename: Patricia Marçal da
authors.initials: PM
authors.lastname: Costa
authors.forename: Paulo Michel Pinheiro
authors.initials: PM
authors.lastname: Ferreira
authors.forename: Vanderlan da Silva
authors.initials: Vda S
authors.lastname: Bolzani
authors.forename: Maysa
authors.initials: M
authors.lastname: Furlan
authors.forename: Vânia Aparecida
authors.initials: VA
authors.lastname: de Freitas Formenton Macedo Dos Santos
authors.forename: Joaquim
authors.initials: J
authors.lastname: Corsino
authors.forename: Manoel Odorico
authors.initials: MO
authors.lastname: de Moraes
authors.forename: Letícia Veras
authors.initials: LV
authors.lastname: Costa-Lotufo
authors.forename: Raquel Carvalho
authors.initials: RC
authors.lastname: Montenegro
authors.forename: Cláudia
authors.initials: C
authors.lastname: Pessoa
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D053938:DNA Fragmentation / Q000187:drug effects; D004264:DNA Topoisomerases, Type I / Q000187:drug effects / Q000378:metabolism; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D029755:Maytenus / Q000737:chemistry*; D009336:Necrosis / Q000378:metabolism; D053978:Pentacyclic Triterpenes; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D018517:Plant Roots; D014315:Triterpenes / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004273:DNA, Neoplasm; D053978:Pentacyclic Triterpenes; D010936:Plant Extracts; D014315:Triterpenes; D004264:DNA Topoisomerases, Type I; C050414:celastrol