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RESEARCH PRODUCT
Induction of apoptosis in a leukemia cell line by triterpene saponins from Albizia adianthifolia
Mohamed HaddadVéronique LaurensMarie Aleth Lacaille-duboissubject
T-LymphocytesClinical BiochemistryPharmaceutical ScienceAlbizziaApoptosisHemolysisBiochemistryJurkat cellsCell LineJurkat Cellschemistry.chemical_compoundDrug DiscoveryTumor Cells CulturedHumansCytotoxic T cellPropidium iodideOleanolic AcidCytotoxicityMolecular BiologyPlants MedicinalDose-Response Relationship DrugbiologyChemistryOrganic ChemistryBiological activitySaponinsbiology.organism_classificationAntineoplastic Agents PhytogenicTriterpenesBiochemistryConcanavalin ACell culturebiology.proteinMolecular MedicineAlbizia adianthifoliadescription
Abstract Triterpenoid saponins, which are present in plants and some marine animals, exert various important pharmacological effects. The present study examines the effects of adianthifoliosides A, B, and D (AdA, AdB, and AdD) together with two prosapogenins (Pro1 and Pro2) obtained from Albizia adianthifolia (Mimosaceae) on human leukemia T-cells (Jurkat cells) and on splenocytes. AdA, AdB, and AdD were found to exhibit a cytotoxic effect on Jurkat cells, whereas the prosapogenins were found to exert a lymphoproliferative effect on this cell type. Furthermore, all tested compounds were found to exert a synergistic lymphoproliferative activity with concanavalin A (ConA) on splenocytes. The concentrations where the saponins were found to be cytotoxic on Jurkat cells are far below the concentration of hemolysis. These results indicate that another mechanism than membrane permeabilization formation is responsible of the cell cytotoxicity. Thus, we demonstrated that at 5 μM for AdA and at 1 μM for AdD, these compounds induce apoptosis in Jurkat cells. Early apoptotic events were detected by flow cytometry analysis by using a double annexin-V-FITC and propidium iodide staining. In addition, a disrupted mitochondrial membrane potential was observed in cells treated with AdA, AdB, and AdD. Furthermore, a DNA ladder was observed when Jurkat cells were incubated with 1 μM AdD for 24 h. By comparison between the biological activities of the native compounds with the prosapogenins, we show in this work the important role of the acylation and esterification by different moieties at C-21 and C-28 of the aglycone (acacic acid) in the apoptosis-inducing capacity. Particularly, the monoterpene-quinovosyl moiety is shown to be important for the induction of apoptosis.
year | journal | country | edition | language |
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2004-09-01 | Bioorganic & Medicinal Chemistry |