| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Laboratory of Leukocyte Biology, Division of Basic Sciences, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, Maryland 21702 [J. M. T., F. W. R., F. V. G.]; Laboratory of Chemoprevention, National Cancer Institute, Bethesda, Maryland 20892 [S-J. K.]; and Intramural Research and Support Program, Science Application International Corporation-Frederick, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, Maryland 21702 [M. C. B-R., T. F.]
Vitamin E succinate (VES) inhibited the proliferation of the estrogen receptor-negative human breast cancer cell line, BT-20, in the G1 phase of the cell cycle. The E2F proteins are integral transcriptional components in the regulation of cell growth. Overexpression of E2F-1 blocked the ability of VES to inhibit BT-20 cell growth, suggesting that VES regulation of E2F-1 activity leads to growth arrest of BT-20 cells. VES, although having little effect on E2F-1 steady-state protein levels, decreased E2F-1 phosphorylation and transactivation activity and increased cyclin A binding to E2F-1. GAL4-E2F-1 deletion mutant studies indicated that cyclin A negatively regulates E2F function. In VES-treated BT-20 cells, the cyclin A protein exhibited reduced kinase activity, which correlated with decreased steady-state levels and binding of cyclin-dependent kinase-2 to cyclin A and increased steady-state levels and binding of p21cip1 to cyclin A and cyclin-dependent kinase-2. The functional consequence of the negative regulatory effect of VES on E2F-1 function was shown by the ability of VES to inhibit the transcriptional activation of an E2F-1 responsive gene, c-myc. These studies show that VES induces growth inhibition of BT-20 cells through a mechanism that involves cyclin A-negative regulation of E2F-mediated transcription.
1 To whom requests for reprints should be addressed. Phone: (301) 846-1442; Fax: (301) 846-6862.
Received 12/13/96. Accepted 5/ 5/97.
This article has been cited by other articles:
|
|
 |
|
  C. G. Havens, A. Ho, N. Yoshioka, and S. F. Dowdy Regulation of Late G1/S Phase Transition and APCCdh1 by Reactive Oxygen Species Mol. Cell. Biol., June 15, 2006; 26(12): 4701 - 4711. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-W. Shiau, J.-W. Huang, D.-S. Wang, J.-R. Weng, C.-C. Yang, C.-H. Lin, C. Li, and C.-S. Chen {alpha}-Tocopheryl Succinate Induces Apoptosis in Prostate Cancer Cells in Part through Inhibition of Bcl-xL/Bcl-2 Function J. Biol. Chem., April 28, 2006; 281(17): 11819 - 11825. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Donapaty, S. Louis, E. Horvath, J. Kun, S. M. Sebti, and M. P. Malafa RRR-{alpha}-Tocopherol succinate down-regulates oncogenic Ras signaling. Mol. Cancer Ther., February 1, 2006; 5(2): 309 - 316. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Stapelberg, N. Gellert, E. Swettenham, M. Tomasetti, P. K. Witting, A. Procopio, and J. Neuzil {alpha}-Tocopheryl Succinate Inhibits Malignant Mesothelioma by Disrupting the Fibroblast Growth Factor Autocrine Loop: MECHANISM AND THE ROLE OF OXIDATIVE STRESS J. Biol. Chem., July 8, 2005; 280(27): 25369 - 25376. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. N. Prasad Multiple Dietary Antioxidants Enhance the Efficacy of Standard and Experimental Cancer Therapies and Decrease Their Toxicity Integr Cancer Ther, December 1, 2004; 3(4): 310 - 322. [Abstract] [PDF]
|
|
|
|
 |
|
 B. Kumar, M. N. Jha, W. C. Cole, J. S. Bedford, and K. N. Prasad D-Alpha-Tocopheryl Succinate (Vitamin E) Enhances Radiation-Induced Chromosomal Damage Levels in Human Cancer Cells, but Reduces it in Normal Cells J. Am. Coll. Nutr., August 1, 2002; 21(4): 339 - 343. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Weber, M. Lu, L. Andera, H. Lahm, N. Gellert, M. W. Fariss, V. Korinek, W. Sattler, D. S. Ucker, A. Terman, et al. Vitamin E Succinate Is a Potent Novel Antineoplastic Agent with High Selectivity and Cooperativity with Tumor Necrosis Factor-related Apoptosis-inducing Ligand (Apo2 Ligand) in Vivo Clin. Cancer Res., March 1, 2002; 8(3): 863 - 869. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. N. Prasad, W. C. Cole, B. Kumar, and K. C. Prasad Scientific Rationale for Using High-Dose Multiple Micronutrients as an Adjunct to Standard and Experimental Cancer Therapies J. Am. Coll. Nutr., October 1, 2001; 20(90005): 450S - 463. [Abstract] [Full Text]
|
|
|
|
 |
|
 F. de Nigris, T. Youssef, S. Ciafre, F. Franconi, V. Anania, G. Condorelli, W. Palinski, and C. Napoli Evidence for Oxidative Activation of c-Myc-Dependent Nuclear Signaling in Human Coronary Smooth Muscle Cells and in Early Lesions of Watanabe Heritable Hyperlipidemic Rabbits : Protective Effects of Vitamin E Circulation, October 24, 2000; 102(17): 2111 - 2117. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. S. McIntyre, K. P. Briski, A. Gapor, and P. W. Sylvester Antiproliferative and Apoptotic Effects of Tocopherols and Tocotrienols on Preneoplastic and Neoplastic Mouse Mammary Epithelial Cells Experimental Biology and Medicine, September 1, 2000; 224(4): 292 - 301. [Abstract] [Full Text]
|
|
|
|
 |
|
 T. J. Moran, S. Gray, C. A. Mikosz, and S. D. Conzen The Glucocorticoid Receptor Mediates a Survival Signal in Human Mammary Epithelial Cells Cancer Res., February 1, 2000; 60(4): 867 - 872. [Abstract] [Full Text]
|
|
|
|
|
|
K. N. Prasad, A. Kumar, V. Kochupillai, and W. C. Cole High Doses of Multiple Antioxidant Vitamins: Essential Ingredients in Improving the Efficacy of Standard Cancer Therapy J. Am. Coll. Nutr., February 1, 1999; 18(1): 13 - 25. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kim, O. Bang, Y. Lee, and S. Kang Production of inducible nitric oxide is required for monocytic differentiation of U937 cells induced by vitamin E-succinate J. Cell Sci., January 2, 1998; 111(4): 435 - 441. [Abstract] [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 |
