Abstract | BACKGROUND AND PROCEDURE: 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:
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Authors | S Fulda, K M Debatin |
Journal | Medical and pediatric oncology
(Med Pediatr Oncol)
Vol. 35
Issue 6
Pg. 616-8
(Dec 2000)
ISSN: 0098-1532 [Print] United States |
PMID | 11107130
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright 2000 Wiley-Liss, Inc. |
Chemical References |
- Antineoplastic Agents, Phytogenic
- Pentacyclic Triterpenes
- Triterpenes
- Betulinic Acid
|
Topics |
- Antineoplastic Agents, Phytogenic
(pharmacology)
- Apoptosis
(drug effects)
- Humans
- Mitochondria
(drug effects)
- Neuroblastoma
(pathology)
- Neuroectodermal Tumors
(pathology)
- Pentacyclic Triterpenes
- Triterpenes
(pharmacology)
- Tumor Cells, Cultured
- Betulinic Acid
|