Inhibitory effect of triptolide on glioblastoma multiforme in vitro.
This study investigated the effect of triptolide, derived from the traditional Chinese herb Tripterygium wilfordii, on the growth of glioblastoma multiforme (GBM) cells. Glioma cell lines U251MG and U87MG and normal human fetal astrocytes were exposed to various concentrations of triptolide, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium and colony formation assays were used to measure cell growth and survival. Cell apoptosis was determined using annexin V. Levels of the oncogenic transformation-related proteins Ras-guanosine triphosphate (Ras-GTP), extracellular signal-regulated kinase (ERK) and Akt were determined by Western blotting. Triptolide caused a dose-dependent decrease in proliferation and increase in apoptosis in the glioma cell lines. Since U87MG has a wildtype p53 gene while U251MG harbours a mutated p53 gene, these results indicate that triptolide induces apoptosis in GBM cells via a p53-independent pathway. Treatment of GBM cells with triptolide attenuated both the Ras/ERK and the Ras/Akt signalling pathways. This could provide a theoretical basis for triptolide treatment in GBM, but further animal studies and clinical research are necessary.
Lin
J
J
College of Life Science and Biotechnology, Jiaotong University, Shanghai, People's Republic of China. jianlinmt@163.com
Chen
L
L
Lin
Z
Z
Zhao
M
M
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004852:Epoxy Compounds / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010616:Phenanthrenes / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D014408:Biomarkers, Tumor; D004224:Diterpenes; D004365:Drugs, Chinese Herbal; D004852:Epoxy Compounds; D010616:Phenanthrenes; D010936:Plant Extracts; C001899:triptolide; D051058:Oncogene Protein v-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D016283:Proto-Oncogene Proteins p21(ras)