[논문]Gelam Honey and Ginger Potentiate the Anti Cancer Effect of 5-FU against HCT 116 Colorectal Cancer Cells

Hakim, Luqman; Alias, Ekram; Makpol, Suzana; Ngah, Wan Zurinah Wan; Morad, Nor Azian; Yusof, Yasmin Anum Mohd

doi:10.7314/apjcp.2014.15.11.4651

[해외논문] Gelam Honey and Ginger Potentiate the Anti Cancer Effect of 5-FU against HCT 116 Colorectal Cancer Cells 원문보기

Asian Pacific journal of cancer prevention : APJCP, v.15 no.11, 2014년, pp.4651 - 4657

Hakim, Luqman (Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia) , Alias, Ekram (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) , Morad, Nor Azian (Centre of Lipids and Engineering and Applied Research, Universiti Teknologi) , Yusof, Yasmin Anum Mohd (Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia)

Abstract ▼ AI-Helper

The development of chemopreventive approaches using a concoction of phytochemicals is potentially viable for combating many types of cancer including colon carcinogenesis. This study evaluated the anti-proliferative effects of ginger and Gelam honey and its efficacy in enhancing the anti-cancer effects of 5-FU (5-fluorouracil) against a colorectal cancer cell line, HCT 116. Cell viability was measured via MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulphenyl)-2H-tetrazolium) assay showing ginger inhibiting the growth of HCT 116 cells more potently ($IC_{50}$ of 3mg/mL) in comparison to Gelam honey ($IC_{50}$ of 75mg/mL). Combined treatment of the two compounds (3mg/mL ginger+75mg/mL Gelam honey) synergistically lowered the $IC_{50}$ of Gelam honey to 22mg/mL. Combination with 35 mg/mL Gelam honey markedly enhanced 5-FU inhibiting effects on the growth of HCT 116 cells. Subsequent analysis on the induction of cellular apoptosis suggested that individual treatment of ginger and Gelam honey produced higher apoptosis than 5-FU alone. In addition, treatment with the combination of two natural compounds increased the apoptotic rate of HCT 116 cells dose-dependently while treatment of either ginger or Gelam honey combined with 5-FU only showed modest changes. Combination index analysis showed the combination effect of both natural compounds to be synergistic in their inhibitory action against HCT 116 colon cancer cells (CI 0.96 < 1). In conclusion, combined treatment of Gelam honey and ginger extract could potentially enhance the chemotherapeutic effect of 5-FU against colorectal cancer.

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제안 방법

To our knowledge, this study is the first to demonstrate the anti cancer potential of Gelam honey by inhibiting the proliferation and inducing apoptosis of HCT 116 colon cancer cells. The most possible mechanism of anti-cancer effect of Gelam honey is by arresting cancer cells at G0/G1 phase and inducing pro apoptotic proteins as demonstrated in colon cancer HCT 15 and HT 29 cells by Jaganathan and Mandal (2009, 2010).

대상 데이터

HCT 116 cell line was obtained from the American Type Culture Collection (Rockville, USA) and was cultured in T-25 flask containing McCoy 5A Medium Modified equipped with L-glutamine (Invitrogen, USA) supplemented with 10% fetal calf serum (FCS) (PAA Laboratories GmbH, Austria), 100U/mL PenicillinStreptomycin (Flowlab, Ausralia), and 100U/mL Amphotericin B (Flowlab, Australia) at 37°C in a humidified atmosphere of 5% CO2 .
Gelam honey was provided by the National Apiary, Department of Agriculture, Batu Pahat, Johor, Malaysia. The honey was sent to SINAGAMA, Malaysian Nuclear Agency for sterilization using the Cobalt-60 source (Model JS10000).
Gelam honey was provided by the National Apiary, Department of Agriculture, Batu Pahat, Johor, Malaysia. The honey was sent to SINAGAMA, Malaysian Nuclear Agency for sterilization using the Cobalt-60 source (Model JS10000). The irradiation process was done at 25kGy and subsequently stored at 4°C for future use.

데이터처리

Data were analyzed using Repeated Measure – OneWay Analysis of Variance (ANOVA) followed by Tukey’s post-hoc tests, and Repeated Measure - Two-Way ANOVA to determine differences between groups.
Statistical analysis was performed using Repeated-Measure ANOVA, followed by Tukey’s Post-Hoc test.
Percentage of viable cells gained from individual and co-treatment of the drug was measured in triplicate (presented as mean±SD, n=3). Statistical analysis was performed using Repeated-Measure Two-way ANOVA, followed by Bonferroni post-tests. A p value of <0.

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