Polyphenol Containing Sorghum Brans Exhibit an Anti-Cancer Effect in Apc Min/+ Mice Treated with Dextran Sodium Sulfate

Int J Mol Sci. 2021 Aug 1;22(15):8286. doi: 10.3390/ijms22158286.

Abstract

Colon cancer (CC) is considered a high-risk cancer in developed countries. Its etiology is correlated with a high consumption of red meat and low consumption of plant-based foods, including whole grains. Sorghum bran is rich in polyphenols. This study aimed to determine whether different high-phenolic sorghum brans suppress tumor formation in a genetic CC rodent model and elucidate mechanisms. Tissue culture experiments used colorectal cancer cell lines SW480, HCT-116 and Caco-2 and measured protein expression, and protein activity. The animal model used in this study was APC Min+/mouse model combined with dextram sodium sulfate. High phenolic sorghum bran extract treatment resulted in the inhibition of proliferation and induced apoptosis in CC cell lines. Treatment with high phenolic sorghum bran extracts repressed TNF-α-stimulated NF-κB transactivation and IGF-1-stimulated PI3K/AKT pathway via the downregulation of β-catenin transactivation. Furthermore, high-phenolic sorghum bran extracts activated AMPK and autophagy. Feeding with high-phenolic sorghum bran for 6 weeks significantly suppressed tumor formation in an APC Min/+ dextran sodium sulfate promoted CC mouse model. Our data demonstrates the potential application of high-phenolic sorghum bran as a functional food for the prevention of CC.

Keywords: AMPK; Apc Min/+ mouse; PI3K; autophagy; colon cancer; high phenolic sorghum bran.

MeSH terms

  • Adenomatous Polyposis Coli Protein / physiology*
  • Animals
  • Apoptosis
  • Cell Proliferation
  • Colorectal Neoplasms / chemically induced
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Dextran Sulfate / toxicity*
  • Disease Models, Animal*
  • Female
  • Humans
  • Male
  • Mice
  • Plant Extracts / pharmacology*
  • Sorghum / chemistry*
  • Tumor Cells, Cultured

Substances

  • Adenomatous Polyposis Coli Protein
  • Plant Extracts
  • adenomatous polyposis coli protein, mouse
  • Dextran Sulfate