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Dauricine induces apoptosis, inhibits proliferation and invasion through inhibiting NF-kappaB signaling pathway in colon cancer cells.
- Source :
-
Journal of cellular physiology [J Cell Physiol] 2010 Oct; Vol. 225 (1), pp. 266-75. - Publication Year :
- 2010
-
Abstract
- Dauricine, a bioactive component of Asiatic Moonseed Rhizome, has been widely used to treat a large number of inflammatory diseases in traditional Chinese medicine. In our study, we demonstrated that dauricine inhibited colon cancer cell proliferation and invasion, and induced apoptosis by suppressing nuclear factor-kappaB (NF-kappaB) activation in a dose- and time-dependent manner. Addition of dauricine inhibited the phosphorylation and degradation of IkappaBalpha, and the phosphorylation and translocation of p65. Moreover, dauricine down-regulated the expression of various NF-kappaB-regulated genes, including genes involved cell proliferation (cyclinD1, COX2, and c-Myc), anti-apoptosis (survivin, Bcl-2, XIAP, and IAP1), invasion (MMP-9 and ICAM-1), and angiogenesis (VEGF). In athymic nu/nu mouse model, we further demonstrated that dauricine significantly suppressed colonic tumor growth. Taken together, our results demonstrated that dauricine inhibited colon cancer cell proliferation, invasion, and induced cell apoptosis by suppressing NF-kappaB activity and the expression profile of its downstream genes. These findings provide evidence for a novel role of dauricine in preventing or treating colon cancer through modulation of NF-kappaB singling pathway.<br /> ((c) 2010 Wiley-Liss, Inc.)
- Subjects :
- Animals
Anti-Inflammatory Agents, Non-Steroidal chemistry
Anti-Inflammatory Agents, Non-Steroidal therapeutic use
Benzylisoquinolines chemistry
Benzylisoquinolines therapeutic use
Caspases metabolism
Cell Cycle drug effects
Cell Line, Tumor
Colonic Neoplasms drug therapy
Extracellular Signal-Regulated MAP Kinases metabolism
Gene Expression Regulation, Neoplastic drug effects
Humans
I-kappa B Proteins metabolism
Mice
Mitogen-Activated Protein Kinase 8 metabolism
Mitogen-Activated Protein Kinase 9 metabolism
Molecular Structure
NF-KappaB Inhibitor alpha
Neoplasm Invasiveness
Neoplasm Transplantation
Poly(ADP-ribose) Polymerases metabolism
Tetrahydroisoquinolines chemistry
Tetrahydroisoquinolines therapeutic use
p38 Mitogen-Activated Protein Kinases metabolism
Anti-Inflammatory Agents, Non-Steroidal pharmacology
Apoptosis drug effects
Benzylisoquinolines pharmacology
Cell Proliferation drug effects
Colonic Neoplasms metabolism
NF-kappa B metabolism
Signal Transduction drug effects
Tetrahydroisoquinolines pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4652
- Volume :
- 225
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of cellular physiology
- Publication Type :
- Academic Journal
- Accession number :
- 20509140
- Full Text :
- https://doi.org/10.1002/jcp.22261