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Triptolide inhibits transcription factor NF-kappaB and induces apoptosis of multiple myeloma cells.

AbstractTriptolide has been reported to be effective in the treatment of auto-immune diseases. This study investigates the cytotoxic function of triptolide on multiple myeloma (MM) cells. We found that triptolide inhibited the proliferation of both RPMI8226 and U266 cells in a dose-dependent manner (10-80 ng/mL). Triptolide induced apoptosis in MM cells through activation of the cystein protease caspase 8, 9 and 3, and subsequent cleavage of the DNA repair enzyme poly (ADP-ribose) polymerase. Apoptosis was confirmed with cell-cycle analysis and annexin V staining. Moreover, triptolide down-regulated nuclear factor (NF)-kappaB activity in MM cell lines. In addition, triptolide also induced chemosensitivity to doxorubicin and suppressed cell proliferation of fresh MM cells. Therefore, triptolide appears to be a potent inducer of apoptosis in myeloma cells, and might have some benefit in the treatment of myeloma patients.
AuthorsLou Yinjun, Jin Jie, Wang Yungui (Affiliation: Department of Hematology, Institute of Hematology, The First Affiliated Hospital of ZheJiang University, Hangzhou, ZheJiang 310003, China.)
JournalLeukemia research (Leuk Res) Vol. 29 Issue 1 Pg. 99-105 (Jan 2005) ISSN: 0145-2126 England
PMID15541481 (Publication Type: Journal Article)
Chemical References
  • Antineoplastic Agents, Alkylating
  • Diterpenes
  • Epoxy Compounds
  • NF-kappa B
  • Phenanthrenes
  • Proteins
  • Transcription Factors
  • triptolide
  • PARP1 protein, human
  • Poly(ADP-ribose) Polymerases
  • CASP8 protein, human
  • CASP9 protein, human
  • Caspase 8
  • Caspase 9
  • Caspases
Topics
  • Antineoplastic Agents, Alkylating (pharmacology)
  • Apoptosis (drug effects)
  • Caspase 8
  • Caspase 9
  • Caspases (metabolism)
  • Cell Proliferation (drug effects)
  • Diterpenes (pharmacology)
  • Enzyme Activation
  • Epoxy Compounds
  • Humans
  • Multiple Myeloma (drug therapy, pathology)
  • NF-kappa B (antagonists & inhibitors)
  • Phenanthrenes (pharmacology)
  • Poly(ADP-ribose) Polymerases
  • Proteins (metabolism)
  • Transcription Factors (antagonists & inhibitors)
  • Tumor Cells, Cultured