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

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.

Wogonoside inhibits cell growth and induces mitochondrial-mediated autophagy-related apoptosis in human colon cancer cells through the PI3K/AKT/mTOR/p70S6K signaling pathway

“…In numerous malignant tumor types, including breast cancer and non-small cell lung cancer, the PI3K/Akt signaling pathway may prevent the death of cancer cells from chemotherapy or radiotherapy-induced apoptosis (12). Selectively inhibiting PI3K or Akt activity to decrease the phosphorylation of Akt may increase the sensitivity of cells towards apoptosis induced by chemotherapy and radiotherapy (23). For lymphoma with high expression levels of Akt, mTOR inhibitors significantly increase the chemotherapy-induced apoptosis rate of cancer cells (24).…”

Awareness of Medical Students at Al-Imam University of the Medical Uses and Benefits of Honey

“…Another research done by a researcher called Hakim T. also supports what Tahir did conclude in his research but he found that GH enhances anti-cancer effect of 5-FU (5-flurouracill) against colorectal cancers (13,14).…”

“…Tahir T. and his colleagues examined the GH on colon cancer cells and they conclude that it may be an effective chemo-preventive and therapeutic strategy for inducing death to colon cancer cells (13,14).…”

Studies of Malaysian Plants in Prevention and Treatment of Colorectal Cancer

“…For instance, Ng et al [46] looked at the potential effects of Piper betle leaf extract to reduce the 5-Fluorouracil dosage required to exert the same cytotoxicity in HT29 and HCT116 cells. Tahir et al [48] studied the combined effects of Zingiber officinale extracts and Gelam honey on viability of HT29 cells. Some researchers have also studied the potential mechanism of the selected species beyond cytotoxicity tests.…”