Active lipids of Ganoderma lucidum spores-induced apoptosis in human leukemia THP-1 cells via MAPK and PI3K pathways

• Published in: Journal of ethnopharmacology 2012-01, Vol.139 (2), p.582-589
• Main Authors: Wang, Jia-He, Zhou, Yi-Jun, Zhang, Meng, Kan, Liang, He, Ping
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Annexin V; Antineoplastic Agents - isolation & purification; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Blotting, Western; c-Jun amino-terminal kinase; Cancer; Caspase inhibitors; Caspase-3; Caspases - metabolism; Cell Survival - drug effects; Dose-Response Relationship, Drug; Enzyme Activation; Enzyme Activators - pharmacology; Extracellular signal-regulated kinase; Extracellular Signal-Regulated MAP Kinases - antagonists & inhibitors; Extracellular Signal-Regulated MAP Kinases - metabolism; Flow Cytometry; Ganoderma lucidum; HL-60 Cells; Humans; Hyperglycemia; Hypertension; JNK Mitogen-Activated Protein Kinases - metabolism; Leukemia; Leukemia - enzymology; Leukemia - pathology; Lipids; Lipids - isolation & purification; Lipids - pharmacology; MAP kinase; MAP Kinase Signaling System - drug effects; MAPK; Mitogen-Activated Protein Kinases - antagonists & inhibitors; Mitogen-Activated Protein Kinases - metabolism; p38 Mitogen-Activated Protein Kinases - metabolism; Phosphatidylinositol 3-Kinase - metabolism; Phosphorylation; Protein Kinase Inhibitors - pharmacology; Proto-Oncogene Proteins c-akt - antagonists & inhibitors; Proto-Oncogene Proteins c-akt - metabolism; Reishi - chemistry; Signal transduction; Spectrophotometry; Spores; Spores, Fungal; THP-1; Time Factors; Traditional Chinese medicine; Western blotting
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2011.11.055

Ganoderma lucidum (Lingzhi) is traditionally drug, which has been traditionally effective used in the treatment of chronic hepatopathy, hypertension, hyperglycemia and cancer. 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. 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. 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.