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

Analhuda Abdullah Tahir,Wan Zurinah Wan Ngah,Noor Azian Murad,Nur Fathiah Abdul Sani,Suzana Makpol,Yasmin Anum Mohd Yusof

doi:10.1186/s12937-015-0015-2

Analhuda Abdullah Tahir, Wan Zurinah Wan Ngah + Show 4 more

Open Access

https://doi.org/10.1186/s12937-015-0015-2

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Abstract

BackgroundThe 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.MethodsThe 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.ResultsThe 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.ConclusionsIn conclusion, the combination of ginger and Gelam honey may be an effective chemopreventive and therapeutic strategy for inducing the death of colon cancer cells.

Highlights

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
Source of ginger extract and Gelam honey The crude ginger extract was supplied by Dr Noor Azian Murad of the Centre of Lipid Engineering and Applied Research (CLEAR), Universiti Teknologi Malaysia
Effect of ginger & Gelam honey alone and in combination on genes in the Ras/ERK & PI3k/AKT pathways Modulation of the gene expression of KRAS, ERK, AKT, Bcl-xL, caspase 9, p65 and IκBα involved in the Ras/ERK

Summary

Introduction

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. Mutations of the KRAS proto-oncogene and any of its downstream elements will lead to abnormal signaling and activation of these pathways, resulting in uncontrolled cell growth [6]. Activation of the PI3K/ AKT pathway has been shown to activate NFκB through phosphorylation of IKK, which in turn

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