Carcinogenesis, Vol. 24, No. 2, 209-216,
February 2003
© 2003 Oxford University Press
CANCER BIOLOGY |
2-Methoxyestradiol interferes with NF
B transcriptional activity in primitive neuroectodermal brain tumors: implications for management
Center for Cancer Causation and Prevention, AMC Cancer Research Center and University of Colorado Comprehensive Cancer Center, Denver, CO 80214, USA and
1 Department of Neuro-Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 431, Houston, TX 77030, USA
Medulloblastoma (MB) is a primitive neuroectodermal tumor (PNET) of the central nervous system (CNS) and the most common malignant primary brain tumor in children. Currently, poor risk and recurrent MB patients are treated with cytotoxic chemotherapy alone or in combination with surgery and irradiation. In order to improve on therapeutic outcome and reduce toxicity of current treatment strategies, new and novel therapeutic agents are needed for MB patients. To that purpose, we have examined the effect of 2-methoxyestradiol (2-ME), an endogenous non-toxic estrogenic metabolite on the growth of three medulloblastoma cell lines (DAOY, D341 and D283); and two high-grade anaplastic astrocytoma/glioblastoma cell lines, U-87MG and T-98-G. We present evidence to show that 2-ME preferentially inhibits the growth of medulloblastoma cells significantly by blocking cell cycle progression predominantly in G2/M phase. 2-ME treatment results in phosphorylation of cdc25C without any significant alterations in the expression of cyclin B1 or p34cdc2. In addition, we observed a decrease in the levels of 14-3-3 proteins following treatment with 2-ME. Furthermore, 2-ME-mediated growth inhibition is accompanied by induction of apoptosis as evidenced by morphological alterations and DNA fragmentation analysis. Of interest is the finding that 2-ME induced apoptosis is not mediated through alterations in the expression of p53 or Bax and that transcriptional activity of NF
B and DNA binding activity is reduced indicating that 2-ME disrupts the NFB signaling pathway. These results suggest that 2-ME may prove to be a useful therapeutic agent in the treatment of PNET brain tumors such as medulloblastoma. In addition, as 2-ME inhibits growth predominantly through G2/M block, it may enhance the effectiveness of radiation therapy.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. A. Maxwell, Z. Li, D. Jaya, S. Ballard, J. Ferrell, and H. Fu 14-3-3{zeta} Mediates Resistance of Diffuse Large B Cell Lymphoma to an Anthracycline-based Chemotherapeutic Regimen J. Biol. Chem., August 14, 2009; 284(33): 22379 - 22389. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Pan, L. W. Bao, and S. D. Merajver Tetrathiomolybdate Inhibits Angiogenesis and Metastasis Through Suppression of the NF{kappa}B Signaling Cascade Mol. Cancer Res., August 1, 2003; 1(10): 701 - 706. [Abstract] [Full Text] [PDF]
|
|