Induction of apoptosis in a leukemia cell line by triterpene saponins from Albizia adianthifolia.
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 microM for AdA and at 1 microM 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 microM AdD for 24h. 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.
Haddad
Mohamed
M
Laboratoire de Pharmacognosie, UMIB EA 3660, Faculté de Pharmacie, Université de Bourgogne, 7 Boulevard Jeanne d'Arc, BP 87900, 21079 Dijon Cedex, France.
Laurens
Véronique
V
Lacaille-Dubois
Marie-Aleth
MA
D031289:Albizzia / Q000737:chemistry*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006461:Hemolysis; D006801:Humans; D019169:Jurkat Cells; D009828:Oleanolic Acid / Q000031:analogs & derivatives*; D010946:Plants, Medicinal / Q000737:chemistry; D012503:Saponins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D013601:T-Lymphocytes / Q000378:metabolism*; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D012503:Saponins; D014315:Triterpenes; C476666:adianthifolioside A; C476667:adianthifolioside B; C026473:prosapogenin; D009828:Oleanolic Acid