Myriadenolide, a labdane diterpene isolated from Alomia myriadenia (asteraceae) induces depolarization of mitochondrial membranes and apoptosis associated with activation of caspases-8, -9, and -3 in Jurkat and THP-1 cells

Exp Cell Res. 2003 Nov 1;290(2):420-6. doi: 10.1016/s0014-4827(03)00350-1.


Myriadenolide is a diterpene that we have recently isolated from the extract of Alomia myriadenia (Asteraceae). Here we show for the first time that myriadenolide has caspase-dependent cytotoxic activity against human leukemia cells from both lymphocytic (Jurkat) and monocytic (THP-1) lineages, because preincubation of Jurkat or THP-1 cells with the broad-spectrum caspase inhibitor z-VAD-fmk completely abrogated cell death. Moreover, the mitochondrial pathway is implicated as mitochondrial depolarization and caspase-9 and caspase-3 activation were observed. Interestingly, caspase-8 and cleavage of the proapoptotic member of the Bcl-2 family BID was also observed during apoptosis induced by myriadenolide, suggesting a role for the caspase-8/BID pathway. However, interference with Fas or TNFR1 signaling did not interfere with apoptosis in our experimental system. Furthermore, pretreatment of cells with the caspase-3 inhibitor DEVD-fmk completely blocked the activation of caspase-8, suggesting that the activation of the caspase-8/BID pathway is part of an amplification loop initiated by caspase-3. Taken together, our results indicate myriadenolide as a novel candidate for the treatment of hematological malignancies.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / metabolism
  • Apoptosis / drug effects*
  • Asteraceae / chemistry*
  • Blotting, Western
  • Caspase 3
  • Caspase 8
  • Caspase 9
  • Caspases / metabolism*
  • Cell Cycle
  • Cytochromes c / metabolism
  • Diterpenes / isolation & purification
  • Diterpenes / pharmacology*
  • Dose-Response Relationship, Drug
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Jurkat Cells / drug effects
  • Jurkat Cells / enzymology
  • Membrane Potentials / drug effects
  • Mitochondria / drug effects*
  • Mitochondria / enzymology
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Receptors, Tumor Necrosis Factor / metabolism
  • Receptors, Tumor Necrosis Factor, Type I
  • Signal Transduction / drug effects
  • fas Receptor / metabolism


  • Antigens, CD
  • Diterpenes
  • Enzyme Inhibitors
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type I
  • fas Receptor
  • Cytochromes c
  • CASP3 protein, human
  • CASP8 protein, human
  • CASP9 protein, human
  • Caspase 3
  • Caspase 8
  • Caspase 9
  • Caspases