| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Brander Cancer Research Institute, New York Medical College, Valhalla, New York 10595 [M. V. B., L. D., F. T., Z. D.], and National Cancer Institute, NIH, Bethesda, Maryland 20892 [R. R., D. L. S., T. F., S. E. B.]
By preventing deacetylation of histones, histone deacetylase inhibitors (HDIs) transcriptionally induce p21. Here we show that the HDIs sodium butyrate (Bu), trichostatin A (TSA) and depsipeptide (FR901228) all induced p21, but only TSA and FR901228 caused mitotic arrest (in addition to arrest in G1 and G2). The ability to cause mitotic arrest correlated with the higher cytotoxicity of these compounds. Although causing mitotic arrest, TSA and FR901228 (unlike paclitaxel) did not affect tubulin polymerization. Unlike FR9012208, TSA caused acetylation of tubulin at lysine 40; both soluble tubulin and microtubules were acetylated. Whereas the induction of p21 reached a maximum by 8 h, tubulin was maximally acetylated after only 1 h of TSA treatment. Tubulin acetylation was detectable after treatment with 12–25 ng/ml TSA although acetylation plateaued at 50 ng/ml TSA, coinciding with G2-M arrest, appearance of cells with a sub-2N DNA content, poly(ADP-ribose) polymerase cleavage, and rapid cell death. We conclude that HDIs have differential effects on non-histone deacetylases and that rapid acetylation of tubulin caused by TSA is a marker of nontranscriptional effects of TSA.
This article has been cited by other articles:
|
|
 |
|
  V. Egler, S. Korur, M. Failly, J.-L. Boulay, R. Imber, M. M. Lino, and A. Merlo Histone Deacetylase Inhibition and Blockade of the Glycolytic Pathway Synergistically Induce Glioblastoma Cell Death Clin. Cancer Res., May 15, 2008; 14(10): 3132 - 3140. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Dai, S. Chen, L. B. Kramer, V. L. Funk, P. Dent, and S. Grant Interactions between Bortezomib and Romidepsin and Belinostat in Chronic Lymphocytic Leukemia Cells Clin. Cancer Res., January 15, 2008; 14(2): 549 - 558. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Brest, M. Gustafsson, A.-K. Mossberg, L. Gustafsson, C. Duringer, A. Hamiche, and C. Svanborg Histone Deacetylase Inhibitors Promote the Tumoricidal Effect of HAMLET Cancer Res., December 1, 2007; 67(23): 11327 - 11334. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Terry-Allison, C. A. Smith, and N. A. DeLuca Relaxed Repression of Herpes Simplex Virus Type 1 Genomes in Murine Trigeminal Neurons J. Virol., November 15, 2007; 81(22): 12394 - 12405. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Camphausen and P. J. Tofilon Inhibition of Histone Deacetylation: A Strategy for Tumor Radiosensitization J. Clin. Oncol., September 10, 2007; 25(26): 4051 - 4056. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. G Catalano, R. Poli, M. Pugliese, N. Fortunati, and G. Boccuzzi Valproic acid enhances tubulin acetylation and apoptotic activity of paclitaxel on anaplastic thyroid cancer cell lines Endocr. Relat. Cancer, September 1, 2007; 14(3): 839 - 845. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Catley, E. Weisberg, T. Kiziltepe, Y.-T. Tai, T. Hideshima, P. Neri, P. Tassone, P. Atadja, D. Chauhan, N. C. Munshi, et al. Aggresome induction by proteasome inhibitor bortezomib and {alpha}-tubulin hyperacetylation by tubulin deacetylase (TDAC) inhibitor LBH589 are synergistic in myeloma cells Blood, November 15, 2006; 108(10): 3441 - 3449. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. C. Dowdy, S. Jiang, X. C. Zhou, X. Hou, F. Jin, K. C. Podratz, and S.-W. Jiang Histone deacetylase inhibitors and paclitaxel cause synergistic effects on apoptosis and microtubule stabilization in papillary serous endometrial cancer cells. Mol. Cancer Ther., November 1, 2006; 5(11): 2767 - 2776. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Olaharski, Z. Ji, J.-Y. Woo, S. Lim, A. E. Hubbard, L. Zhang, and M. T. Smith The Histone Deacetylase Inhibitor Trichostatin A Has Genotoxic Effects in Human Lymphoblasts In Vitro Toxicol. Sci., October 1, 2006; 93(2): 341 - 347. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Imre, V. Gekeler, A. Leja, T. Beckers, and M. Boehm Histone Deacetylase Inhibitors Suppress the Inducibility of Nuclear Factor-{kappa}B by Tumor Necrosis Factor-{alpha} Receptor-1 Down-regulation. Cancer Res., May 15, 2006; 66(10): 5409 - 5418. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Sankaranarayanapillai, W. P. Tong, D. S. Maxwell, A. Pal, J. Pang, W. G. Bornmann, J. G. Gelovani, and S. M. Ronen Detection of histone deacetylase inhibition by noninvasive magnetic resonance spectroscopy Mol. Cancer Ther., May 1, 2006; 5(5): 1325 - 1334. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Zhao, S. Lu, L. Wu, G. Chai, H. Wang, Y. Chen, J. Sun, Y. Yu, W. Zhou, Q. Zheng, et al. Acetylation of p53 at Lysine 373/382 by the Histone Deacetylase Inhibitor Depsipeptide Induces Expression of p21Waf1/Cip1. Mol. Cell. Biol., April 1, 2006; 26(7): 2782 - 2790. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-N. Li, Q. Shu, J. M.-F. Su, L. Perlaky, S. M. Blaney, and C. C. Lau Valproic acid induces growth arrest, apoptosis, and senescence in medulloblastomas by increasing histone hyperacetylation and regulating expression of p21Cip1, CDK4, and CMYC Mol. Cancer Ther., December 1, 2005; 4(12): 1912 - 1922. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. J. Chung, S. Lee, E. A. Sausville, Q. Ryan, J. E. Karp, I. Gojo, W. G. Telford, M.-J. Lee, H. S. Kong, and J. B. Trepel Histone Deacetylase Inhibitor Pharmacodynamic Analysis by Multiparameter Flow Cytometry Ann. Clin. Lab. Sci., October 1, 2005; 35(4): 397 - 406. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Stimson, M. G. Rowlands, Y. M. Newbatt, N. F. Smith, F. I. Raynaud, P. Rogers, V. Bavetsias, S. Gorsuch, M. Jarman, A. Bannister, et al. Isothiazolones as inhibitors of PCAF and p300 histone acetyltransferase activity Mol. Cancer Ther., October 1, 2005; 4(10): 1521 - 1532. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Acharya, A. Sparreboom, J. Venitz, and W. D. Figg Rational Development of Histone Deacetylase Inhibitors as Anticancer Agents: A Review Mol. Pharmacol., October 1, 2005; 68(4): 917 - 932. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. V. Blagosklonny, S. Trostel, G. Kayastha, Z. N. Demidenko, L. T. Vassilev, L. Y. Romanova, S. Bates, and T. Fojo Depletion of Mutant p53 and Cytotoxicity of Histone Deacetylase Inhibitors Cancer Res., August 15, 2005; 65(16): 7386 - 7392. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. V. Nome, A. Bratland, G. Harman, O. Fodstad, Y. Andersson, and A. H. Ree Cell cycle checkpoint signaling involved in histone deacetylase inhibition and radiation-induced cell death Mol. Cancer Ther., August 1, 2005; 4(8): 1231 - 1238. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. N. Bhalla Epigenetic and Chromatin Modifiers As Targeted Therapy of Hematologic Malignancies J. Clin. Oncol., June 10, 2005; 23(17): 3971 - 3993. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Rahmani, E. Reese, Y. Dai, C. Bauer, S. G. Payne, P. Dent, S. Spiegel, and S. Grant Coadministration of Histone Deacetylase Inhibitors and Perifosine Synergistically Induces Apoptosis in Human Leukemia Cells through Akt and ERK1/2 Inactivation and the Generation of Ceramide and Reactive Oxygen Species Cancer Res., March 15, 2005; 65(6): 2422 - 2432. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Doi, H. Soda, M. Oka, J. Tsurutani, T. Kitazaki, Y. Nakamura, M. Fukuda, Y. Yamada, S. Kamihira, and S. Kohno The histone deacetylase inhibitor FR901228 induces caspase-dependent apoptosis via the mitochondrial pathway in small cell lung cancer cells Mol. Cancer Ther., November 1, 2004; 3(11): 1397 - 1402. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Camphausen, T. Scott, M. Sproull, and P. J. Tofilon Enhancement of Xenograft Tumor Radiosensitivity by the Histone Deacetylase Inhibitor MS-275 and Correlation with Histone Hyperacetylation Clin. Cancer Res., September 15, 2004; 10(18): 6066 - 6071. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-H. Park, Y. Jung, T. Y. Kim, S. G. Kim, H.-S. Jong, J. W. Lee, D.-K. Kim, J.-S. Lee, N. K. Kim, T.-Y. Kim, et al. Class I Histone Deacetylase-Selective Novel Synthetic Inhibitors Potently Inhibit Human Tumor Proliferation Clin. Cancer Res., August 1, 2004; 10(15): 5271 - 5281. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Nguyen, W. D. Schrump, G. A. Chen, W. Tsai, P. Nguyen, J. B. Trepel, and D. S. Schrump Abrogation of p21 Expression by Flavopiridol Enhances Depsipeptide-Mediated Apoptosis in Malignant Pleural Mesothelioma Cells Clin. Cancer Res., March 1, 2004; 10(5): 1813 - 1825. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Camphausen, W. Burgan, M. Cerra, K. A. Oswald, J. B. Trepel, M.-J. Lee, and P. J. Tofilon Enhanced Radiation-Induced Cell Killing and Prolongation of {gamma}H2AX Foci Expression by the Histone Deacetylase Inhibitor MS-275 Cancer Res., January 1, 2004; 64(1): 316 - 321. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Fuino, P. Bali, S. Wittmann, S. Donapaty, F. Guo, H. Yamaguchi, H.-G. Wang, P. Atadja, and K. Bhalla Histone deacetylase inhibitor LAQ824 down-regulates Her-2 and sensitizes human breast cancer cells to trastuzumab, taxotere, gemcitabine, and epothilone B Mol. Cancer Ther., October 1, 2003; 2(10): 971 - 984. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Catley, E. Weisberg, Y.-T. Tai, P. Atadja, S. Remiszewski, T. Hideshima, N. Mitsiades, R. Shringarpure, R. LeBlanc, D. Chauhan, et al. NVP-LAQ824 is a potent novel histone deacetylase inhibitor with significant activity against multiple myeloma Blood, October 1, 2003; 102(7): 2615 - 2622. [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 |
