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Ganoderic acids suppress growth and angiogenesis by modulating the NF-κB signaling pathway in breast cancer cells.

Abstract
It has been demonstrated that ganoderma acids suppress growth, angiogenesis and invasiveness of highly invasive and metastatic breast cancer cells in vitro and vivo. However, the mechanism of action of ganoderma acids in breast cancer remains unknown. In the present study, we looked into the effect of ganoderic acid Me (GA-Me) on cellular phenotypes and tumor growth in the MDA-MB-231 breast cancer cell line. The results indicated the GA-Me inhibited nuclear factor kappaB (NF-κB) activity at 24 h in MDA-MB-231 cells. When MDAMB- 231 cells were stimulated with tumor necrosis factor-alpha (TNF-α), the inhibitory effects of GA-Me were still maintained. We demonstrated that GA-Me inhibited proliferation and invasion and induced apoptosis in MDA-MB-231 cells via suppressing the NF-κB activity. However, GA-Me did not inhibit the phosphorylation and degradation of IkappaB-α (IkB-α). GA-Me down-regulated the expression of various NF-κB-regulated genes including genes involved in cell proliferation (c-Myc and cyclin D1), anti-apoptosis (Bcl-2), invasion (MMP-9) and angiogenesis (VEGF, interleukin (IL)-6 and -8). I.P. administration of GA-Me inhibited tumor growth of MDA-MB-231 cells in vivo. Our results demonstrated that GA-Me inhibited proliferation, angiogenesis, invasion and induced apoptosis in MDA-MB-231 cells via suppressing NF-κB activity and the expression profile of its downstream genes. These findings provide evidence for a novel role of GA-Me in the prevention and treatment of breast cancer by its ability to modulate the NF-κB signaling pathway.
AuthorsFunian Li, Yu Wang, Xingang Wang, Jianguo Li, Haining Cui, Min Niu
JournalInternational journal of clinical pharmacology and therapeutics (Int J Clin Pharmacol Ther) Vol. 50 Issue 10 Pg. 712-21 (Oct 2012) ISSN: 0946-1965 [Print] Germany
PMID22762853 (Publication Type: Journal Article)
Chemical References
  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Interleukin-8
  • NF-kappa B
  • Transcription Factor RelA
  • Triterpenes
  • ganoderic acid Me
Topics
  • Angiogenesis Inhibitors (pharmacology)
  • Animals
  • Antineoplastic Agents (pharmacology)
  • Apoptosis (drug effects)
  • Breast Neoplasms (drug therapy, pathology)
  • Cell Line, Tumor
  • Cell Movement (drug effects)
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Interleukin-8 (metabolism)
  • Male
  • Mice
  • Mice, Inbred BALB C
  • NF-kappa B (antagonists & inhibitors, physiology)
  • Signal Transduction (drug effects)
  • Transcription Factor RelA (metabolism)
  • Triterpenes (pharmacology)

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