Clinical Cancer Research CR Balducci Advances in Breast Cancer
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
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Huang, Y.
Right arrow Articles by Davidson, N. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Huang, Y.
Right arrow Articles by Davidson, N. E.
Clinical Cancer Research Vol. 9, 2769-2777, July 2003
© 2003 American Association for Cancer Research

Experimental Therapeutics, Preclinical Pharmacology

A Novel Polyamine Analog Inhibits Growth and Induces Apoptosis in Human Breast Cancer Cells1

Yi Huang, Erin R. Hager, Dawn L. Phillips, Valerie R. Dunn, Amy Hacker, Benjamin Frydman, John A. Kink, Aldonia L. Valasinas, Venodhar K. Reddy, Laurence J. Marton, Robert A. Casero, Jr. and Nancy E. Davidson2

The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231 [Y. H., E. R. H., D. L. P., A. H., R. A. C., N. E. D.]; SLIL Biomedical Corp., Madison, Wisconsin 53711 [B. F., J. A. K., A. L. V., V. K. R., L. J. M.]; and Department of Surgery, Howard University, Washington, DC 20060 [V. R. D.]

Polyamine analogs have demonstrated considerable activity against many important solid tumor models including breast cancer. However, the precise mechanisms of antitumor activities of polyamine analogs are not entirely understood. The cytotoxicity of a newly developed polyamine analog compound, SL11144, against human breast cancer was assessed. Treatment of human breast cancer cell lines in culture with SL11144 decreased cell proliferation and induced programmed cell death in a time- and dose-dependent manner. SL11144 also profoundly inhibited the growth of MDA-MB-231 xenografts in host nude mice without overt toxic effects. Treatment of MDA-MB-435 cells with SL11144 led to the release of cytochrome c from mitochondria into cytosol, activation of caspase-3, and poly(ADP-ribose) polymerase cleavage. SL11144 decreased Bcl-2 and increased Bax protein levels in MDA-MB-231 cells. Furthermore, activator protein 1 transcriptional factor family member c-Jun was up-regulated by SL11144 in MDA-MB-435 and MDA-MB-231 cells, but not in MCF7 cells. In addition, significant inhibition of ornithine decarboxylase activity and a decrease in polyamine pools were demonstrated. These results demonstrate that the novel polyamine analog SL11144 has effective antineoplastic action against human breast cancer cells in vitro and in vivo and that multiple apoptotic mechanisms are associated with its cytotoxic effect in specific human breast cancer cell lines.




This article has been cited by other articles:


Home page
 Cancer Res.Home page
J. S. Carew, S. T. Nawrocki, V. K. Reddy, D. Bush, J. E. Rehg, A. Goodwin, J. A. Houghton, R. A. Casero Jr, L. J. Marton, and J. L. Cleveland
The Novel Polyamine Analogue CGC-11093 Enhances the Antimyeloma Activity of Bortezomib
Cancer Res., June 15, 2008; 68(12): 4783 - 4790.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
A. Pledgie-Tracy, M. D. Sobolewski, and N. E. Davidson
Sulforaphane induces cell type-specific apoptosis in human breast cancer cell lines
Mol. Cancer Ther., March 1, 2007; 6(3): 1013 - 1021.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Y. Huang, J. C. Keen, A. Pledgie, L. J. Marton, T. Zhu, S. Sukumar, B. H. Park, B. Blair, K. Brenner, R. A. Casero Jr, et al.
Polyamine Analogues Down-regulate Estrogen Receptor {alpha} Expression in Human Breast Cancer Cells
J. Biol. Chem., July 14, 2006; 281(28): 19055 - 19063.
[Abstract] [Full Text] [PDF]

Home page
 J BiochemHome page
Y. Wang and R. A. Casero Jr.
Mammalian Polyamine Catabolism: A Therapeutic Target, a Pathological Problem, or Both?
J. Biochem., January 1, 2006; 139(1): 17 - 25.
[Abstract] [Full Text] [PDF]

Home page
 Mol Cancer ResHome page
Y. Huang, J. C. Keen, E. Hager, R. Smith, A. Hacker, B. Frydman, A. L. Valasinas, V. K. Reddy, L. J. Marton, R. A. Casero Jr., et al.
Regulation of Polyamine Analogue Cytotoxicity by c-Jun in Human MDA-MB-435 Cancer Cells
Mol. Cancer Res., February 1, 2004; 2(2): 81 - 88.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
A. C. Wolff, D. K. Armstrong, J. H. Fetting, M. K. Carducci, C. D. Riley, J. F. Bender, R. A. Casero Jr., and N. E. Davidson
A Phase II Study of the Polyamine Analog N1,N11-Diethylnorspermine (DENSpm) Daily for Five Days Every 21 Days in Patients with Previously Treated Metastatic Breast Cancer
Clin. Cancer Res., December 1, 2003; 9(16): 5922 - 5928.
[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
Copyright © 2003 by the American Association for Cancer Research.