Dauricine induces apoptosis, inhibits proliferation and invasion through inhibiting NF-kappaB signaling pathway in colon cancer cells.
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.
Yang
Zhengfeng
Z
The Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
Li
Chenghai
C
Wang
Xiu
X
Zhai
Chunyan
C
Yi
Zhengfang
Z
Wang
Lei
L
Liu
Bisheng
B
Du
Bing
B
Wu
Huihui
H
Guo
Xizhi
X
Liu
Mingyao
M
Li
Dali
D
Luo
Jian
J
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D044182:Benzylisoquinolines / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D051379:Mice; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism; D048056:Mitogen-Activated Protein Kinase 9 / Q000378:metabolism; D015394:Molecular Structure; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D044005:Tetrahydroisoquinolines / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D044182:Benzylisoquinolines; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; D044005:Tetrahydroisoquinolines; D000072000:NF-KappaB Inhibitor alpha; C035934:dauricine; D011065:Poly(ADP-ribose) Polymerases; D048056:Mitogen-Activated Protein Kinase 9; D048049:Extracellular Signal-Regulated MAP Kinases; D048055:Mitogen-Activated Protein Kinase 8; D048051:p38 Mitogen-Activated Protein Kinases; D020169:Caspases