| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Experimental Therapeutics, Molecular Targets, and Chemical Biology |
1 Institut National de la Santé et de la Reserche Médicale U601, Département de Recherche en Cancérologie, Nantes, France; 2 Cancer Research, Institut de Recherches Servier, Croissy/Seine, France; and 3 Université de Rennes 1, Synthèse et Electrosynthèse Organiques, Centre National de la Reserche Scientifique UMR 6510, Rennes, France
Requests for reprints: Philippe Juin, Institut National de la Santé et de la Reserche Médicale U601, Département de Recherche en Cancérologie, 9 Quai Moncousu, 44035 Nantes Cedex 035, France. Phone: 33-24-008-4083; Fax: 33-24-008-4082; E-mail: Philippe.Juin{at}univ-nantes.fr.
A functional imbalance between proapoptotic Bax and antiapoptotic Bcl-2 is likely to participate in the resistance of cancer cells to therapy. We show here that ethyl 2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate (HA14-1), a small organic compound recently proposed to function as an inhibitor of Bcl-2, increases the sensitivity of human glioblastoma cells to radiotherapy and chemotherapy. This sensitizing effect is lost if Bcl-2 expression, but not Bcl-xL expression, is knocked down or if cells only express a mutant of Bax that does not interact with Bcl-2. This points to a specific Bcl-2 inhibitory function of HA14-1 and implies that it selectively involves hindrance of Bcl-2 binding to Bax, which HA14-1 inhibits in cell-free assays and in cells in receipt of an apoptotic stimulation. Moreover, HA14-1, in combination with a cytotoxic treatment, slows down the growth of glioblastoma in vivo. Thus, the inhibition of Bcl-2 achieved by HA14-1 might improve treatment outcome. (Cancer Res 2006; 66(5): 2757-64)
This article has been cited by other articles:
|
|
 |
|
  T. Gallenne, F. Gautier, L. Oliver, E. Hervouet, B. Noel, J. A. Hickman, O. Geneste, P.-F. Cartron, F. M. Vallette, S. Manon, et al. Bax activation by the BH3-only protein Puma promotes cell dependence on antiapoptotic Bcl-2 family members J. Cell Biol., April 20, 2009; 185(2): 279 - 290. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. H. Kang and C. P. Reynolds Bcl-2 Inhibitors: Targeting Mitochondrial Apoptotic Pathways in Cancer Therapy Clin. Cancer Res., February 15, 2009; 15(4): 1126 - 1132. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. D. Zeitlin, I. J. Zeitlin, and J. E. Nor Expanding Circle of Inhibition: Small-Molecule Inhibitors of Bcl-2 as Anticancer Cell and Antiangiogenic Agents J. Clin. Oncol., September 1, 2008; 26(25): 4180 - 4188. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Konopleva, J. Watt, R. Contractor, T. Tsao, D. Harris, Z. Estrov, W. Bornmann, H. Kantarjian, J. Viallet, I. Samudio, et al. Mechanisms of Antileukemic Activity of the Novel Bcl-2 Homology Domain-3 Mimetic GX15-070 (Obatoclax) Cancer Res., May 1, 2008; 68(9): 3413 - 3420. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S. Ziegler, A. L. Kung, and M. W. Kieran Anti-Apoptosis Mechanisms in Malignant Gliomas J. Clin. Oncol., January 20, 2008; 26(3): 493 - 500. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Ren, Z. Chen, L. Chen, N. T. Woods, G. W. Reuther, J. Q. Cheng, H.-g. Wang, and J. Wu Shp2E76K Mutant Confers Cytokine-independent Survival of TF-1 Myeloid Cells by Up-regulating Bcl-XL J. Biol. Chem., December 14, 2007; 282(50): 36463 - 36473. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
