title: Piplartine induces inhibition of leukemia cell proliferation triggering both apoptosis and necrosis pathways.
abstract: Piplartine {5,6-dihydro-1-[1-oxo-3-(3,4,5-trimethoxyphenyl)-2-propenyl]-2(1H)pyridinone} is an alkaloid/amide component of Piper species. The purpose of the present study was to examine the antiproliferative effects of piplartine on human leukemia cell lines HL-60, K562, Jukart, and Molt-4 using the trypan blue exclusion method, as well as the effect of piplartine on DNA synthesis. The viability of all human leukemia cell lines were not affected by piplartine after 6 h, 9 h, and 12 h exposure, whereas a steady decline was seen after an exposure time of 24 h. The antiproliferative activity of piplartine seemed to be related to the inhibition of DNA synthesis, as revealed by the reduction of 5-bromo-2'-deoxyuridine (BrdU) incorporation after 24h of incubation. Piplartine-mediated reduction in cell number was associated with an increasing number of dead cells at a concentration of 10 microg/ml. These findings were corroborated by morphologic analysis. However, at the lowest concentration (2.5 microg/ml), piplartine-treated cells exhibited typical apoptotic morphological changes. The increase in caspase-3 activity was also observed in lysates of piplartine-treated cells (2.5 microg/ml). Our findings suggest that piplartine can suppress leukemia growth and reduce cell survival, triggering both apoptosis and/or necrosis, depending on the concentration used.
authors.affiliation: Departamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará, Caixa Postal 3157, 60430-270 Fortaleza, Ceará, Brazil.
authors.forename: Daniel Pereira
authors.initials: DP
authors.lastname: Bezerra
authors.forename: Gardenia Carmen Gadelha
authors.initials: GC
authors.lastname: Militão
authors.forename: Fernanda Oliveira
authors.initials: FO
authors.lastname: de Castro
authors.forename: Cláudia
authors.initials: C
authors.lastname: Pessoa
authors.forename: Manoel Odorico
authors.initials: MO
authors.lastname: de Moraes
authors.forename: Edilberto Rocha
authors.initials: ER
authors.lastname: Silveira
authors.forename: Mary Anne Sousa
authors.initials: MA
authors.lastname: Lima
authors.forename: Francisca Juliana Martins
authors.initials: FJ
authors.lastname: Elmiro
authors.forename: Letícia Veras
authors.initials: LV
authors.lastname: Costa-Lotufo
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D066298:In Vitro Techniques; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy*; D015458:Leukemia, T-Cell / Q000188:drug therapy / Q000473:pathology; D008856:Microscopy, Fluorescence; D009000:Monocytes / Q000187:drug effects; D009336:Necrosis / Q000473:pathology; D009690:Nucleic Acid Conformation / Q000187:drug effects; D031701:Piper / Q000737:chemistry; D010881:Piperidones / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004273:DNA, Neoplasm; D010881:Piperidones; C498077:piperlongumine; D004247:DNA; D053148:Caspase 3