Publication: Retama monosperma n-hexane extract induces cell cycle arrest and extrinsic pathway-dependent apoptosis in Jurkat cells
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2014-01-24
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BioMed Central (BMC)
Abstract
Background: Retama monosperma L. (Boiss.) or Genista monosperma L. (Lam.), locally named as R'tam, is an annual and spontaneous plant belonging to the Fabaceae family. In Morocco, Retama genus is located in desert regions and across the Middle Atlas and it has been widely used in traditional medicine in many countries. In this study, we show that Retama monosperma hexane extract presents significant anti-leukemic effects against human Jurkat cells. Methods: Human Jurkat cells, together with other cell lines were screened with different concentrations of Retama monosperma hexane extract at different time intervals. Growth inhibition was determined using luminescent-based viability assays. Cell cycle arrest and apoptosis were measured by flow cytometry analysis. Combined caspase 3 and 7 activities were measured using luminometric caspase assays and immunoblots were performed to analyze expression of relevant pro-and anti-apoptotic proteins. GC-MS were used to determine the chemical constituents of the active extract. Results: Retama monosperma hexane extract (Rm-HE) showed significant cytotoxicity against Jurkat cells, whereas it proved to be essentially ineffective against both normal mouse fibroblasts (NIH3T3) and normal lymphocytes (TK-6). Cytometric analysis indicated that Rm-HE promoted cell cycle arrest and apoptosis induction accompanied by DNA damage induction indicated by an increase in p-H2A. X levels. Rm-HE induced apoptosis was partially JNK-dependent and characterized by an increase in Fas-L levels together with activation of caspases 8, 3, 7 and 9, whereas neither the pro-apoptotic nor anti-apoptotic mitochondrial membrane proteins analyzed were significantly altered. Chemical identification analysis indicated that a-linolenic acid, campesterol, stigmasterol and sitosterol were the major bioactive components within the extract. Conclusions: Our data suggest that bioactive compounds present in Rm-HE show significant anti leukemic activity inducing cell cycle arrest and cell death that operates, at least partially, through the extrinsic apoptosis pathway.
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MeSH Terms
Cholesterol Humans Phytosterols Cell Death MAP Kinase Kinase 4 Signal Transduction Apoptosis Regulatory Proteins Leukemia, T-Cell Mice NIH 3T3 Cells Antineoplastic Agents, Phytogenic Phytotherapy Plant Extracts Fabaceae Caspases Cell Proliferation Sitosterols Cell Cycle Checkpoints Apoptosis Animals Caspase 3 Stigmasterol Fas Ligand Protein Jurkat Cells alpha-Linolenic Acid
DeCS Terms
Ácido alfa-Linolénico Estigmasterol Apoptosis Sitoesteroles Caspasa 3 Fitoterapia Antineoplásicos Fitogénicos Fabaceae Células Jurkat Puntos de Control del Ciclo Celular Proteína Ligando Fas Transducción de Señal Animales Caspasas Proliferación Celular Leucemia de Células T Muerte Celular Células 3T3 NIH Extractos Vegetales MAP Quinasa Quinasa 4 Colesterol Humanos Fitosteroles Proteínas Reguladoras de la Apoptosis Ratones
Bibliographic citation
Belayachi L, Aceves-Luquero C, Merghoub N, Bakri Y, Fernández De Mattos S, Amzazi S, et al. Retama monosperma n-hexane extract induces cell cycle arrest and extrinsic pathway-dependent apoptosis in Jurkat cells. BMC Complement Altern Med. 2014 Jan 24;14:38.