Journal article
A Novel Polyamine Analog Inhibits Growth and Induces Apoptosis in Human Breast Cancer Cells1
Clinical cancer research, Vol.9(7), pp.2769-2777
07/01/2003
PMCID: PMC3625930
PMID: 12855657
Abstract
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.
Details
- Title: Subtitle
- A Novel Polyamine Analog Inhibits Growth and Induces Apoptosis in Human Breast Cancer Cells1
- Creators
- Yi HuangErin R. HagerDawn L. PhillipsValerie R. DunnAmy HackerBenjamin FrydmanJohn A. KinkAldonia L. ValasinasVenodhar K. ReddyLaurence J. MartonRobert A. CaseroNancy E. Davidson
- Resource Type
- Journal article
- Publication Details
- Clinical cancer research, Vol.9(7), pp.2769-2777
- PMID
- 12855657
- PMCID
- PMC3625930
- ISSN
- 1078-0432
- eISSN
- 1557-3265
- Grant note
- P50 CA088843 || CA / National Cancer Institute : NCI
- Language
- English
- Date published
- 07/01/2003
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984383292102771
Metrics
13 Record Views