Mechanism of Chemoprevention against Colon Cancer Cells Using Combined Gelam Honey and Ginger Extract via mTOR and Wnt/β-catenin Pathways

Asian Pac J Cancer Prev. 2015;16(15):6549-56. doi: 10.7314/apjcp.2015.16.15.6549.

Abstract

The PI3K-Akt-mTOR, Wnt/β-catenin and apoptosis signaling pathways have been shown to be involved in genesis of colorectal cancer (CRC). The aim of this study was to elucidate whether combination of Gelam honey and ginger might have chemopreventive properties in HT29 colon cancer cells by modulating the mTOR, Wnt/β-catenin and apoptosis signaling pathways. Treatment with Gelam honey and ginger reduced the viability of the HT29 cells dose dependently with IC50 values of 88 mg/ml and 2.15 mg/ml respectively, their while the combined treatment of 2 mg/ml of ginger with 31 mg/ml of Gelam honey inhibited growth of most HT29 cells. Gelam honey, ginger and combination induced apoptosis in a dose dependent manner with the combined treatment exhibiting the highest apoptosis rate. The combined treatment downregulated the gene expressions of Akt, mTOR, Raptor, Rictor, β-catenin, Gsk3β, Tcf4 and cyclin D1 while cytochrome C and caspase 3 genes were shown to be upregulated. In conclusion, the combination of Gelam honey and ginger may serve as a potential therapy in the treatment of colorectal cancer through inhibiton of mTOR, Wnt/β catenin signaling pathways and induction of apoptosis pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Anticarcinogenic Agents / pharmacology*
  • Apoptosis / drug effects
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics
  • Carrier Proteins / genetics
  • Caspase 3 / genetics
  • Cell Survival / drug effects
  • Chemoprevention
  • Cyclin D1 / genetics
  • Cytochromes c / genetics
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • Gene Expression / drug effects
  • Ginger*
  • Glycogen Synthase Kinase 3 / genetics
  • Glycogen Synthase Kinase 3 beta
  • HT29 Cells
  • Honey*
  • Humans
  • Inhibitory Concentration 50
  • Melaleuca
  • Plant Extracts / pharmacology*
  • Proto-Oncogene Proteins c-akt / genetics
  • Rapamycin-Insensitive Companion of mTOR Protein
  • Regulatory-Associated Protein of mTOR
  • TOR Serine-Threonine Kinases / genetics*
  • TOR Serine-Threonine Kinases / metabolism
  • Transcription Factor 4
  • Transcription Factors / genetics
  • Up-Regulation / drug effects
  • Wnt Signaling Pathway / drug effects*
  • beta Catenin / genetics

Substances

  • Adaptor Proteins, Signal Transducing
  • Anticarcinogenic Agents
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Carrier Proteins
  • Plant Extracts
  • RICTOR protein, human
  • RPTOR protein, human
  • Rapamycin-Insensitive Companion of mTOR Protein
  • Regulatory-Associated Protein of mTOR
  • TCF4 protein, human
  • Transcription Factor 4
  • Transcription Factors
  • beta Catenin
  • Cyclin D1
  • Cytochromes c
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Proto-Oncogene Proteins c-akt
  • Glycogen Synthase Kinase 3
  • Caspase 3