| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Experimental Therapeutics, Molecular Targets, and Chemical Biology |
1 Department of Urology, 2 Interdisciplinary Graduate Program in Immunology, and 3 Prostate Cancer Research Program, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, Iowa
Requests for reprints: Thomas S. Griffith, Department of Urology, University of Iowa, 3204 Medical Education and Biomedical Research Facility, 375 Newton Road, Iowa City, IA 52242-1089. Phone: 319-335-7581; Fax: 319-353-4556; E-mail: thomas-griffith{at}uiowa.edu.
Urothelial carcinoma of the bladder accounts for 
5% of all cancer deaths in humans. The large majority of tumors are superficial at diagnosis and, after local surgical therapy, have a high rate of local recurrence and progression. Current treatments extend time to recurrence but do not alter disease survival. The objective of the present study was to investigate the tumoricidal potential of combining the apoptosis-inducing protein tumor necrosis factor–related apoptosis inducing ligand (TRAIL) with histone deacetylase inhibitors (HDACi) against TRAIL-resistant bladder tumor cells. Pretreatment with HDACi at nontoxic doses, followed by incubation with TRAIL, resulted in a marked increase in TRAIL-induced apoptosis of T24 cells but showed no significant increase in toxicity to SV40 immortalized normal human uroepithelial cell-1. HDAC inhibition, especially with sodium butyrate and trichostatin A, led to increased TRAIL-R2 gene transcription that correlated with increased TRAIL-R2 surface expression. The increased TRAIL-R2 levels also resulted in accelerated death-inducing signaling complex (DISC) formation, caspase activation, and loss of mitochondrial membrane potential, which all contributed to the increase in tumor cell death. Collectively, these results show the therapeutic potential of combining HDAC inhibition with TRAIL as an alternative treatment for bladder cancer. (Cancer Res 2006; 66(1): 499-507)
This article has been cited by other articles:
|
|
 |
|
  A. J. Frew, R. K. Lindemann, B. P. Martin, C. J. P. Clarke, J. Sharkey, D. A. Anthony, K.-M. Banks, N. M. Haynes, P. Gangatirkar, K. Stanley, et al. Combination therapy of established cancer using a histone deacetylase inhibitor and a TRAIL receptor agonist PNAS, August 12, 2008; 105(32): 11317 - 11322. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Zhou, G.-D. Lu, C.-S. Ong, C.-N. Ong, and H.-M. Shen Andrographolide sensitizes cancer cells to TRAIL-induced apoptosis via p53-mediated death receptor 4 up-regulation Mol. Cancer Ther., July 1, 2008; 7(7): 2170 - 2180. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Miyanaga, A. Gemma, R. Noro, K. Kataoka, K. Matsuda, M. Nara, T. Okano, M. Seike, A. Yoshimura, A. Kawakami, et al. Antitumor activity of histone deacetylase inhibitors in non-small cell lung cancer cells: development of a molecular predictive model Mol. Cancer Ther., July 1, 2008; 7(7): 1923 - 1930. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Kamat, G. Sethi, and B. B. Aggarwal Curcumin potentiates the apoptotic effects of chemotherapeutic agents and cytokines through down-regulation of nuclear factor-{kappa}B and nuclear factor-{kappa}B-regulated gene products in IFN-{alpha}-sensitive and IFN-{alpha}-resistant human bladder cancer cells Mol. Cancer Ther., March 1, 2007; 6(3): 1022 - 1030. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. G.E. de Vries, J. A. Gietema, and S. de Jong Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Pathway and Its Therapeutic Implications Clin. Cancer Res., April 15, 2006; 12(8): 2390 - 2393. [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 |
