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Berberine inhibits the proliferation of colon cancer cells by inactivating Wnt/β-catenin signaling.

Abstract
Colon cancer is one of the most common malignancies, mainly initiated by the abnormal activation of Wnt/β-catenin signaling. In this study, we investigated the proliferation inhibitory effect of berberine on colon cancer cells and the molecular basis underlying this effect. With the viability, apoptosis and cell cycle assay, we demonstrated that berberine can inhibit proliferation, induce apoptosis and cell cycle arrest in colon cancer cells. In in vivo investigation, we demonstrated that berberine can prevent the colon cancer formation initiated by dimethylhydrazine (DMH) and dextran sodium sulfate (DSS) in rats. We employed western blotting, reverse transcription and polymerase chain reaction, special antagonist, overexpression and knockdown techniques to dissect the possible molecular mechanisms mediating the function of berberine. We found that the protein levels of β-catenin in the nucleus and cytoplasm were all reduced after treating the colon cancer cells with berberine, and this may not result from accelerating the degradation of β-catenin in the cytoplasm, but from inhibiting the mRNA expression of β-catenin. Our results indicate that berberine can be a potential chemoprevention and chemotherapy agent for human colon cancer by targeting Wnt/β-catenin signaling.
AuthorsKe Wu, Qiujun Yang, Yuqin Mu, Longyang Zhou, Yinzi Liu, Qixin Zhou, Baicheng He
JournalInternational journal of oncology (Int J Oncol) Vol. 41 Issue 1 Pg. 292-8 (Jul 2012) ISSN: 1791-2423 [Electronic] Greece
PMID22469784 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anticarcinogenic Agents
  • Antineoplastic Agents, Phytogenic
  • Dimethylhydrazines
  • beta Catenin
  • Berberine
  • Dextran Sulfate
  • Luciferases, Firefly
  • CASP3 protein, human
  • Caspase 3
Topics
  • Adenocarcinoma (chemically induced, pathology, prevention & control)
  • Animals
  • Anticarcinogenic Agents (pharmacology, therapeutic use)
  • Antineoplastic Agents, Phytogenic (pharmacology, therapeutic use)
  • Apoptosis (drug effects)
  • Berberine (pharmacology, therapeutic use)
  • Caspase 3 (metabolism)
  • Cell Proliferation (drug effects)
  • Cell Survival (drug effects)
  • Colonic Neoplasms (chemically induced, pathology, prevention & control)
  • Dextran Sulfate
  • Dimethylhydrazines
  • Female
  • G1 Phase Cell Cycle Checkpoints (drug effects)
  • Gene Expression (drug effects)
  • Genes, Reporter
  • HCT116 Cells
  • Humans
  • Luciferases, Firefly (biosynthesis, genetics)
  • Promoter Regions, Genetic
  • Rats
  • Rats, Sprague-Dawley
  • Wnt Signaling Pathway (drug effects)
  • beta Catenin (genetics, metabolism)

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