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

  • Wee, Lee Heng (Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia) ;
  • Morad, Noor Azian (Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia) ;
  • Aan, Goon Jo (Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia) ;
  • Makpol, Suzana (Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia) ;
  • Ngah, Wan Zurinah Wan (Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia) ;
  • Yusof, Yasmin Anum Mohd (Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia)
  • Published : 2015.10.06

Abstract

The PI3K-Akt-mTOR, $Wnt/{\beta}$-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, $Wnt/{\beta}$-catenin and apoptosis signaling pathways. Treatment with Gelam honey and ginger reduced the viability of the HT29 cells dose dependently with $IC_{50}$ 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, ${\beta}$-catenin, $Gsk3{\beta}$, 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, $Wnt/{\beta}$ catenin signaling pathways and induction of apoptosis pathway.

Keywords

mTOR;$Wnt/{\beta}$ catenin;apoptosis;combination;HT29 colon cancer cells

Acknowledgement

Supported by : Universiti Kebangsaan

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