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

Tahir AA, Sani NF, Murad NA, Makpol S, Ngah WZ, Yusof YA - Nutr J (2015)

Bottom Line: 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.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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, 56000, Kuala Lumpur, Malaysia. analbaik@gmail.com.

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.

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Related in: MedlinePlus

Effects of ginger and Gelam honey on apoptosis of HT29 cells. The apoptotic effects of single and combined treatments with ginger and Gelam honey were determined by Cell Death Detection ELISA after 24 hours. Data are presented as the mean ± SEM from three independent experiments. a(p < 0.05) significant compared to control, b(p < 0.05) significant compared to 2.5 mg/ml of ginger, c(p < 0.05) significant compared to 5.0 mg/ml of ginger, d(p < 0.05) significant compared to 7.5 mg/ml of ginger, e(p < 0.05) significant compared to 40 mg/ml of Gelam honey, f(p < 0.05) significant compared to 80 mg/ml of Gelam honey, g(p < 0.05) significant compared to 100 mg/ml of Gelam honey, h(p < 0.05) significant compared to combination of 3 mg/ml ginger and 10 mg/ml Gelam honey, i(p < 0.05) significant compared to combination of 3 mg/ml ginger and 30 mg/ml Gelam honey.
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Fig3: Effects of ginger and Gelam honey on apoptosis of HT29 cells. The apoptotic effects of single and combined treatments with ginger and Gelam honey were determined by Cell Death Detection ELISA after 24 hours. Data are presented as the mean ± SEM from three independent experiments. a(p < 0.05) significant compared to control, b(p < 0.05) significant compared to 2.5 mg/ml of ginger, c(p < 0.05) significant compared to 5.0 mg/ml of ginger, d(p < 0.05) significant compared to 7.5 mg/ml of ginger, e(p < 0.05) significant compared to 40 mg/ml of Gelam honey, f(p < 0.05) significant compared to 80 mg/ml of Gelam honey, g(p < 0.05) significant compared to 100 mg/ml of Gelam honey, h(p < 0.05) significant compared to combination of 3 mg/ml ginger and 10 mg/ml Gelam honey, i(p < 0.05) significant compared to combination of 3 mg/ml ginger and 30 mg/ml Gelam honey.

Mentions: As illustrated in Figure 3, treatment with ginger elicited a dose-dependent increase in DNA fragmentation that was higher compared to treatment with honey, indicating a higher rate of apoptosis. Interestingly, when 3 mg/ml of ginger was combined with 50 mg/ml of honey, a synergistic increase in the rate of apoptosis was seen compared to treatment with honey alone.Figure 3


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

Tahir AA, Sani NF, Murad NA, Makpol S, Ngah WZ, Yusof YA - Nutr J (2015)

Effects of ginger and Gelam honey on apoptosis of HT29 cells. The apoptotic effects of single and combined treatments with ginger and Gelam honey were determined by Cell Death Detection ELISA after 24 hours. Data are presented as the mean ± SEM from three independent experiments. a(p < 0.05) significant compared to control, b(p < 0.05) significant compared to 2.5 mg/ml of ginger, c(p < 0.05) significant compared to 5.0 mg/ml of ginger, d(p < 0.05) significant compared to 7.5 mg/ml of ginger, e(p < 0.05) significant compared to 40 mg/ml of Gelam honey, f(p < 0.05) significant compared to 80 mg/ml of Gelam honey, g(p < 0.05) significant compared to 100 mg/ml of Gelam honey, h(p < 0.05) significant compared to combination of 3 mg/ml ginger and 10 mg/ml Gelam honey, i(p < 0.05) significant compared to combination of 3 mg/ml ginger and 30 mg/ml Gelam honey.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4390091&req=5

Fig3: Effects of ginger and Gelam honey on apoptosis of HT29 cells. The apoptotic effects of single and combined treatments with ginger and Gelam honey were determined by Cell Death Detection ELISA after 24 hours. Data are presented as the mean ± SEM from three independent experiments. a(p < 0.05) significant compared to control, b(p < 0.05) significant compared to 2.5 mg/ml of ginger, c(p < 0.05) significant compared to 5.0 mg/ml of ginger, d(p < 0.05) significant compared to 7.5 mg/ml of ginger, e(p < 0.05) significant compared to 40 mg/ml of Gelam honey, f(p < 0.05) significant compared to 80 mg/ml of Gelam honey, g(p < 0.05) significant compared to 100 mg/ml of Gelam honey, h(p < 0.05) significant compared to combination of 3 mg/ml ginger and 10 mg/ml Gelam honey, i(p < 0.05) significant compared to combination of 3 mg/ml ginger and 30 mg/ml Gelam honey.
Mentions: As illustrated in Figure 3, treatment with ginger elicited a dose-dependent increase in DNA fragmentation that was higher compared to treatment with honey, indicating a higher rate of apoptosis. Interestingly, when 3 mg/ml of ginger was combined with 50 mg/ml of honey, a synergistic increase in the rate of apoptosis was seen compared to treatment with honey alone.Figure 3

Bottom Line: 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.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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, 56000, Kuala Lumpur, Malaysia. analbaik@gmail.com.

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.

Show MeSH
Related in: MedlinePlus