title: Inhibition of tumor cellular proteasome activity by triptolide extracted from the Chinese medicinal plant 'thunder god vine'.
abstract: OBJECTIVE
  The molecular mechanisms of triptolide responsible for its antitumor properties are not yet fully understood. The ubiquitin/proteasome system is an important pathway of protein degradation in cells. This study investigated whether triptolide may inhibit proteasomal activity and induce apoptosis in human cancer cells.
  
  
  METHODS
  In vitro proteasome inhibition was measured by incubation of a purified 20S proteasome with triptolide. Human breast and prostate cancer cell lines were also treated with different doses of triptolide for different times, followed by measurement of proteasome inhibition (levels of the chymotrypsin-like activity, ubiquitinated proteins and three well-known proteasome target proteins, p27, IκB-α and Bax) and apoptosis induction (caspase-3 activity and PARP cleavage).
  
  
  RESULTS
  Triptolide did not inhibit the chymotrypsin-like activity of purified 20S proteasome. However, treatment of triptolide was able to cause decreased levels of cellular proteasomal chymotrypsin-like activity and accumulation of ubiquitinated proteins and three well-known proteasome target proteins in human breast and prostate cancer cells, associated with apoptosis induction.
  
  
  CONCLUSIONS
  It is possible that at least one of metabolites of triptolide has proteasome-inhibitory activity.
authors.affiliation: Department of Pathophysiology, Guangzhou Medical University, Guangzhou, Guangdong 510082, China.
authors.forename: Li
authors.initials: L
authors.lastname: Lu
authors.forename: Jyoti
authors.initials: J
authors.lastname: Kanwar
authors.forename: Sara
authors.initials: S
authors.lastname: Schmitt
authors.forename: Qiuzhi Cindy
authors.initials: QC
authors.lastname: Cui
authors.forename: Chuanyin
authors.initials: C
authors.lastname: Zhang
authors.forename: Cong
authors.initials: C
authors.lastname: Zhao
authors.forename: Q Ping
authors.initials: QP
authors.lastname: Dou
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D004852:Epoxy Compounds / Q000494:pharmacology; D005260:Female; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D008297:Male; D000072000:NF-KappaB Inhibitor alpha; D010616:Phenanthrenes / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D061988:Proteasome Inhibitors; D014407:Tumor Cells, Cultured; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D018906:Antineoplastic Agents, Alkylating; D004224:Diterpenes; D004852:Epoxy Compounds; D020672:I-kappa B Proteins; C000606204:NFKBIA protein, human; D010616:Phenanthrenes; D061988:Proteasome Inhibitors; D025801:Ubiquitin; D000072000:NF-KappaB Inhibitor alpha; D050760:Cyclin-Dependent Kinase Inhibitor p27; C001899:triptolide; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3