title: Evaluation of lignan (-)-cubebin extracted from Piper cubeba on human colon adenocarcinoma cells (HT29).
abstract: The dibenzylbutyrolactone lignan (-)-cubebin, which is extracted from the seeds of the pepper Piper cubeba, has shown promise as an anti-inflammatory, analgesic, leishmanicidal, antiproliferative, and trypanocidal compound. Given the therapeutic potential of (-)-cubebin, this study aimed to investigate its safety profile by analyzing cytotoxicity, mutagenicity, cell proliferation kinetics, induction of apoptosis, and expression of pro-apoptotic genes in human colon adenocarcinoma cells (HT29) exposed to (-)-cubebin. MTT cytotoxicity assays demonstrated that (-)-cubebin was cytotoxic only at 280 µM, whereas it was not cytotoxic at 2.8, 14, or 28 µM. Data demonstrated that (-)-cubebin was not mutagenic as evidenced by a micronucleus (MN) assay, did not alter cell-growth kinetics over 4 d, and showed absence of induced apoptosis after 24 h. Further, CASP8 and CASP9 gene expression was not markedly changed in HT29 cells exposed to 28 µM or 70 µM (-)-cubebin for 12 h. Based on our observations, (-)-cubebin was cytotoxic at a concentration of 280 µM, suggesting that the use of this concentration should be avoided. However, lower concentrations exerted no apparent damaging effects, indicating that this lignan is safe to use for pharmacological purposes at certain concentrations.
authors.affiliation: a Universidade Estadual de Londrina , Londrina, Paraná , Brazil.
authors.forename: Andressa Megumi
authors.initials: AM
authors.lastname: Niwa
authors.affiliation: a Universidade Estadual de Londrina , Londrina, Paraná , Brazil.
authors.forename: Natalia Aparecida
authors.initials: NA
authors.lastname: de Paula
authors.affiliation: a Universidade Estadual de Londrina , Londrina, Paraná , Brazil.
authors.forename: Diogo Campos
authors.initials: DC
authors.lastname: Vesenick
authors.affiliation: a Universidade Estadual de Londrina , Londrina, Paraná , Brazil.
authors.forename: Daniele
authors.initials: D
authors.lastname: Sartori
authors.affiliation: b Universidade Estadual Paulista , Marília, São Paulo , Brazil.
authors.forename: Edson Luis
authors.initials: EL
authors.lastname: Maistro
authors.affiliation: c Universidade Estadual Paulista , Botucatu, São Paulo , Brazil.
authors.forename: Lúcia Regina
authors.initials: LR
authors.lastname: Ribeiro
authors.affiliation: a Universidade Estadual de Londrina , Londrina, Paraná , Brazil.
authors.forename: Mário Sérgio
authors.initials: MS
authors.lastname: Mantovani
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053181:Caspase 8 / Q000096:biosynthesis; D053453:Caspase 9 / Q000096:biosynthesis; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004247:DNA / Q000187:drug effects; D019073:HT29 Cells; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D015162:Micronucleus Tests; D031701:Piper / Q000737:chemistry*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017705:Lignans; D004247:DNA; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053181:Caspase 8; D053453:Caspase 9; C433065:cubebin