title: Beta-escin, a natural triterpenoid saponin from Chinese horse chestnut seeds, depresses HL-60 human leukaemia cell proliferation and induces apoptosis.
abstract: Beta-escin, a natural triterpenoid saponin isolated from the seed of the horse chestnut, is known to generate a wide variety of biochemical and pharmacological effects. The purpose of the present study was to examine the apoptotic and antiproliferative activity of beta-escin in HL-60 human acute myeloid leukaemia cells. Antiproliferative activity was examined by soft agar colony assay and the trypan blue exclusion method. Apoptotic activity was evaluated by morphological analysis, annexin V analysis, DNA fragmentation analysis and flow cytometry cell cycle analysis. The results showed that beta-escin caused a significant inhibition of HL-60 cell proliferation in a dose- and time-dependent manner. Morphological evidence of apoptosis, including vacuolization, apoptotic nuclei fragmentation and apoptotic body formation, was observed in cells treated with 30 microg mL(-1) of beta-escin for 24, 48 and 72 h. A significant increase in the population of annexin V+ and PI- cells (early apoptotic) among the total cells was observed in cells treated with beta-escin (30-50 microg mL(-1)) for 24 h (P<0.001). Typical DNA ladders, DNA with a unit length of about 180 bp, were detected in cells treated with beta-escin (30-50 microg mL(-1)) for 48 h by agarose gel electrophoresis. Flow cytometry cell cycle analysis revealed that beta-escin (30-50 microg mL(-1)) induced G1-S arrest and led to a significant accumulation of the sub-G1 population in HL-60 cells (P<0.05). Taken together, the results demonstrate that beta-escin is a potent natural inhibitor of cell proliferation and inducer of apoptosis in HL-60 acute myeloid leukaemia cells. The results indicate that beta-escin may be a useful candidate agent for exploring potential antileukaemic drugs.
authors: Institute of Chinese Herbal Medicine, College of Pharmaceutical Science, Zhejiang University, Hangzhou 310058, China. niuyangping@hotmail.com
authors: Yang P
authors: YP
authors: Niu
authors: Li M
authors: LM
authors: Wu
authors: Yan L
authors: YL
authors: Jiang
authors: Wen X
authors: WX
authors: Wang
authors: Lian D
authors: LD
authors: Li
mesh_terms: D031319:Aesculus / Q000737:chemistry*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004928:Escin / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy; D016196:S Phase / Q000187:drug effects; D012639:Seeds; D013997:Time Factors
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004928:Escin