Combined ginger extract & Gelam honey modulate Ras/ERK and PI3K/AKT pathway genes in colon cancer HT29 cells

Nutr J. 2015 Apr 1;14:31. doi: 10.1186/s12937-015-0015-2.

Abstract

Background: The interconnected Ras/ERK and PI3K/AKT pathways play a central role in colorectal tumorigenesis, and they are targets for elucidating mechanisms involved in attempts to induce colon cancer cell death. Both ginger (Zingiber officinale) and honey have been shown to exhibit anti-tumor and anti-inflammation properties against many types of cancer, including colorectal cancer. However, there are currently no reports showing the combined effect of these two dietary compounds in cancer growth inhibition. The aim of this study was to evaluate the synergistic effect of crude ginger extract and Gelam honey in combination as potential cancer chemopreventive agents against the colorectal cancer cell line HT29.

Methods: The cells were divided into 4 groups: the first group represents HT29 cells without treatment, the second and third groups were cells treated singly with either ginger or Gelam honey, respectively, and the last group represents cells treated with ginger and Gelam honey combined.

Results: The results of MTS assay showed that the IC50 of ginger and Gelam honey alone were 5.2 mg/ml and 80 mg/ml, respectively, whereas the IC50 of the combination treatment was 3 mg/ml of ginger plus 27 mg/ml of Gelam honey with a combination index of < 1, suggesting synergism. Cell death in response to the combined ginger and Gelam honey treatment was associated with the stimulation of early apoptosis (upregulation of caspase 9 and IκB genes) accompanied by downregulation of the KRAS, ERK, AKT, Bcl-xL, NFkB (p65) genes in a synergistic manner.

Conclusions: In conclusion, the combination of ginger and Gelam honey may be an effective chemopreventive and therapeutic strategy for inducing the death of colon cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects*
  • Apoptosis / genetics
  • Caspase 9 / genetics
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / pathology
  • Down-Regulation / drug effects
  • Drug Therapy, Combination / methods
  • Gene Expression / drug effects
  • Ginger / chemistry*
  • HT29 Cells
  • Honey*
  • Humans
  • Inflammation / drug therapy
  • Inflammation / genetics
  • MAP Kinase Signaling System / drug effects*
  • MAP Kinase Signaling System / genetics
  • Oncogene Protein v-akt / genetics
  • Phytotherapy / methods*
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology
  • Plant Preparations / chemistry
  • Plant Preparations / pharmacology
  • Protein Serine-Threonine Kinases / genetics
  • Protein Tyrosine Phosphatases / genetics
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins p21(ras)
  • Treatment Outcome
  • Up-Regulation / drug effects
  • bcl-X Protein / genetics
  • ras Proteins / genetics

Substances

  • Antineoplastic Agents
  • BCL2L1 protein, human
  • KRAS protein, human
  • Plant Extracts
  • Plant Preparations
  • Proto-Oncogene Proteins
  • bcl-X Protein
  • Oncogene Protein v-akt
  • Protein Serine-Threonine Kinases
  • NF-kappa B kinase
  • B59 protein, human
  • Protein Tyrosine Phosphatases
  • Caspase 9
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins