Studies on calcium dependence reveal multiple modes of action for triptolide

Chem Biol. 2005 Dec;12(12):1259-68. doi: 10.1016/j.chembiol.2005.09.009.


Triptolide, a diterpene triepoxide isolated from the traditional Chinese medicinal vine Trypterygium wilfordii hook f., has been shown to induce rapid apoptosis in a myriad of cancer cell lines and inhibit NFkappaB transactivation. To understand further the general cellular mechanisms for this therapeutically relevant natural product, binding and biological activities were assessed. Studies showed that triptolide binding was saturable, reversible, and primarily localized to cell membranes. Depletion of calcium enhanced overall binding while differentially modulating biological function. Furthermore, triptolide's structural moieties demonstrated variability in the regulation of cell death versus inhibition of NFkappaB transactivation. These results implicate triptolide in the manipulation of at least two distinct cellular pathways with differing requirements for calcium and effective triptolide concentration in order to elicit each particular biological function.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Alkylating / chemistry
  • Antineoplastic Agents, Alkylating / metabolism*
  • Antineoplastic Agents, Alkylating / pharmacology*
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / metabolism*
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Binding, Competitive / drug effects
  • Calcium / pharmacology
  • Calcium / physiology*
  • Calcium-Binding Proteins / metabolism
  • Cell Line, Tumor
  • Cell Membrane / metabolism
  • Diterpenes / chemistry
  • Diterpenes / metabolism*
  • Diterpenes / pharmacology*
  • Epoxy Compounds
  • HeLa Cells
  • Humans
  • NF-kappa B / metabolism
  • Phenanthrenes / chemistry
  • Phenanthrenes / metabolism*
  • Phenanthrenes / pharmacology*
  • Transcriptional Activation


  • Antineoplastic Agents, Alkylating
  • Antineoplastic Agents, Phytogenic
  • Calcium-Binding Proteins
  • Diterpenes
  • Epoxy Compounds
  • NF-kappa B
  • Phenanthrenes
  • triptolide
  • Calcium