title: Active lipids of Ganoderma lucidum spores-induced apoptosis in human leukemia THP-1 cells via MAPK and PI3K pathways.
abstract: BACKGROUND
  Ganoderma lucidum (Lingzhi) is traditionally drug, which has been traditionally effective used in the treatment of chronic hepatopathy, hypertension, hyperglycemia and cancer.
  
  
  METHODS
  THP-1 and HL-60 apoptosis induced by active lipids of Ganoderma lucidum spores was quantified by flow cytometry using FITC-conjugated annexin V and PI; MAPK and Akt were measured by Western blot, and caspase-3, -8 and -9 activities were also detected by spectrophotometric assay.
  
  
  RESULTS
  Our results showed that active lipids of Ganoderma lucidum spores decreased phosphorylation-ERK1/2 (P-ERK1/2), P-Akt and increased P-JNK1/2, but did not affect expressions of P-p38 MAPK in THP-1 cells. Moreover, treatment of THP-1 cells with active lipids of Ganoderma lucidum spores resulted in activation of caspase-3, -8 and -9. Furthermore, LY294002 (Akt inhibitor) or PD98059 (ERK1/2 inhibitor) significantly enhanced active lipids of Ganoderma lucidum spores-induced apoptosis in THP-1 cells, whereas caspase inhibitors or SP600125 (JNK inhibitor), decreased apoptosis in THP-1 cells.
  
  
  CONCLUSIONS
  Taken together, our study for the first time suggests that active lipids of Ganoderma lucidum spores is able to enhance apoptosis in THP-1 cells, at least in part, through inhibition of ERK1/2, Akt and activation of JNK1/2 signaling pathways. Moreover, it also triggers caspase-3, -8 and -9 activation mediated apoptotic induction.
authors.affiliation: Department of Geriatrics, Shengjing Hospital of China Medical University, Shenyang, China. wangjh1@sj-hospital.org
authors.forename: Jia-He
authors.initials: JH
authors.lastname: Wang
authors.forename: Yi-Jun
authors.initials: YJ
authors.lastname: Zhou
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.forename: Liang
authors.initials: L
authors.lastname: Kan
authors.forename: Ping
authors.initials: P
authors.lastname: He
mesh_terms: D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D020536:Enzyme Activators / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007938:Leukemia / Q000201:enzymology* / Q000473:pathology; D008055:Lipids / Q000302:isolation & purification / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D020940:Reishi / Q000737:chemistry; D013053:Spectrophotometry; D013172:Spores, Fungal; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D020536:Enzyme Activators; D008055:Lipids; D047428:Protein Kinase Inhibitors; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020169:Caspases