Betulinic acid induces apoptosis through a direct effect on mitochondria in neuroectodermal tumors

Med Pediatr Oncol. 2000 Dec;35(6):616-8. doi: 10.1002/1096-911x(20001201)35:6<616::aid-mpo27>;2-n.


Background and procedure: We identified BetA as a new cytotoxic agent active against neuroectodermal tumor cells including neuroblastoma, medulloblastoma, glioblastoma and Ewing sarcoma cells, representing the most common solid tumors of childhood.

Results: BetA induced apoptosis by a direct effect on mitochondria independent of accumulation of wild-type p53 protein and independent of death-inducing ligand/receptor systems such as CD95. Mitochondrial perturbations on treatment with BetA resulted in the release of soluble apoptogenic factors such as cytochrome c or AIF from mitochondria into the cytosol, where they induced activation of caspases. Overexpression of the anti-apoptotic proteins Bcl-2 or Bcl-X(L) that blocked loss of the mitochondrial membrane potential and cytochrome c release from mitochondria also conferred resistance to BetA. Most importantly, BetA exhibited potent antitumor activity on neuroblastoma cells resistant to CD95- or doxorubicin-triggered apoptosis and on primary tumor cells from patients with neuroectodermal tumors.

Conclusions: Thus, BetA may be a promising new agent in the treatment of neuroectodermal tumors including neuroblastoma in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Betulinic Acid
  • Humans
  • Mitochondria / drug effects*
  • Neuroblastoma / pathology*
  • Neuroectodermal Tumors / pathology*
  • Pentacyclic Triterpenes
  • Triterpenes / pharmacology*
  • Tumor Cells, Cultured


  • Antineoplastic Agents, Phytogenic
  • Pentacyclic Triterpenes
  • Triterpenes
  • Betulinic Acid