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.

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.

Thus, BetA may be a promising new agent in the treatment of neuroectodermal tumors including neuroblastoma in vivo. Med. Pediatr. Oncol. 35:616–618, 2000. © 2000 Wiley‐Liss, Inc.