Calcium prevents tumorigenesis in a mouse model of colorectal cancer

PLoS One. 2011;6(8):e22566. doi: 10.1371/journal.pone.0022566. Epub 2011 Aug 17.


Background and aim: Calcium has been proposed as a mediator of the chemoprevention of colorectal cancer (CRC), but the comprehensive mechanism underlying this preventive effect is not yet clear. Hence, we conducted this study to evaluate the possible roles and mechanisms of calcium-mediated prevention of CRC induced by 1,2-dimethylhydrazine (DMH) in mice.

Methods: For gene expression analysis, 6 non-tumor colorectal tissues of mice from the DMH + Calcium group and 3 samples each from the DMH and control groups were hybridized on a 4×44 K Agilent whole genome oligo microarray, and selected genes were validated by real-time polymerase chain reaction (PCR). Functional analysis of the microarray data was performed using KEGG and Gene Ontology (GO) analyses. Hub genes were identified using Pathway Studio software.

Results: The tumor incidence rates in the DMH and DMH + Calcium groups were 90% and 40%, respectively. Microarray gene expression analysis showed that S100a9, Defa20, Mmp10, Mmp7, Ptgs2, and Ang2 were among the most downregulated genes, whereas Per3, Tef, Rnf152, and Prdx6 were significantly upregulated in the DMH + Calcium group compared with the DMH group. Functional analysis showed that the Wnt, cell cycle, and arachidonic acid pathways were significantly downregulated in the DMH + Calcium group, and that the GO terms related to cell differentiation, cell cycle, proliferation, cell death, adhesion, and cell migration were significantly affected. Forkhead box M1 (FoxM1) and nuclear factor kappa-B (NF-κB) were considered as potent hub genes.

Conclusion: In the DMH-induced CRC mouse model, comprehensive mechanisms were involved with complex gene expression alterations encompassing many altered pathways and GO terms. However, how calcium regulates these events remains to be studied.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1,2-Dimethylhydrazine
  • Animals
  • Basic-Leucine Zipper Transcription Factors / genetics
  • Calcium / administration & dosage
  • Calcium / pharmacology*
  • Calgranulin B / genetics
  • Colorectal Neoplasms / chemically induced
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / prevention & control*
  • Disease Models, Animal
  • Female
  • Forkhead Box Protein M1
  • Forkhead Transcription Factors / genetics
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Regulatory Networks
  • Matrix Metalloproteinase 10 / genetics
  • Mice
  • Mice, Inbred ICR
  • NF-kappa B / genetics
  • Oligonucleotide Array Sequence Analysis
  • Period Circadian Proteins / genetics
  • Peroxiredoxin VI / genetics
  • Real-Time Polymerase Chain Reaction
  • Ribonuclease, Pancreatic / genetics


  • Basic-Leucine Zipper Transcription Factors
  • Calgranulin B
  • Forkhead Box Protein M1
  • Forkhead Transcription Factors
  • Foxm1 protein, mouse
  • NF-kappa B
  • Per3 protein, mouse
  • Period Circadian Proteins
  • Tef protein, mouse
  • Peroxiredoxin VI
  • Prdx6 protein, mouse
  • Ang2 protein, mouse
  • Ribonuclease, Pancreatic
  • Matrix Metalloproteinase 10
  • 1,2-Dimethylhydrazine
  • Calcium