Phyllanthus urinaria induces the Fas receptor/ligand expression and ceramide-mediated apoptosis in HL-60 cells.
Phyllanthus urinaria (P. urinaria), a widely used herb medicine, was tested for the anticancer effect on human myeloid leukemia cells in this study. The water extract of P. urinaria induced the apoptosis of HL-60 cells as demonstrated by morphological change, DNA fragmentation and increased caspase-3 activity. However, normal human peripheral mononuclear cells remained viable under the same treatment. The P. urinaria-induced apoptosis of HL-60 cells was associated with the increased Bax gene expression and decreased Bcl-2 gene expression. In addition, the gene expressions of Fas receptor and Fas ligand, but not p53, were also induced in HL-60 cells dose- and time-dependently. The inhibitor of ceramide synthase, fumonisin B1, completely suppressed the apoptosis induced by P. urinaria and this inhibitory effect of fumonisin B1 could be eliminated by the addition of ceramide. It indicated that the activity of ceramide synthase is critical for the P. urinaria-induced apoptosis in HL-60 cells. The P. urinaria-induced apoptosis in HL-60 cells is mediated through a ceramide-related pathway.
Huang
Sheng-Teng
ST
Chinese Herbal Pharmacy, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan, ROC.
Yang
Rong-Chi
RC
Chen
Min-Yi
MY
Pang
Jong-Hwei S
JH
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002518:Ceramides / Q000494:pharmacology*; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D053222:Fas Ligand Protein; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019254:Genes, bcl-2 / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D009000:Monocytes / Q000187:drug effects; D015345:Oligonucleotide Probes; D010088:Oxidoreductases / Q000037:antagonists & inhibitors; D029803:Phyllanthus / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D051028:bcl-2-Associated X Protein; D019014:fas Receptor / Q000096:biosynthesis*
D000972:Antineoplastic Agents, Phytogenic; C494826:BAX protein, human; D002518:Ceramides; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D015345:Oligonucleotide Probes; D010936:Plant Extracts; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012334:RNA, Neoplasm; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; D010088:Oxidoreductases; C108138:dihydroceramide desaturase; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases