title: Combined ginger extract & Gelam honey modulate Ras/ERK and PI3K/AKT pathway genes in colon cancer HT29 cells.
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.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, 56000, Kuala Lumpur, Malaysia. analbaik@gmail.com.
authors.forename: Analhuda Abdullah
authors.initials: AA
authors.lastname: Tahir
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, 56000, Kuala Lumpur, Malaysia. nurfasni@gmail.com.
authors.forename: Nur Fathiah Abdul
authors.initials: NF
authors.lastname: Sani
authors.affiliation: Centre of Lipid Engineering and Applied Research (CLEAR), Universiti Teknologi Malaysia, Jalan Semarak, 50480, Kuala Lumpur, Malaysia. azian@ic.utm.my.
authors.forename: Noor Azian
authors.initials: NA
authors.lastname: Murad
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, 56000, Kuala Lumpur, Malaysia. suzanamakpol@yahoo.com.
authors.forename: Suzana
authors.initials: S
authors.lastname: Makpol
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, 56000, Kuala Lumpur, Malaysia. wwanzurinah@yahoo.com.
authors.forename: Wan Zurinah Wan
authors.initials: WZ
authors.lastname: Ngah
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, 56000, Kuala Lumpur, Malaysia. rahmatyasmin@yahoo.com.
authors.forename: Yasmin Anum Mohd
authors.initials: YA
authors.lastname: Yusof
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D053453:Caspase 9 / Q000235:genetics; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects; D004359:Drug Therapy, Combination / Q000379:methods; D015870:Gene Expression / Q000187:drug effects; D020939:Zingiber officinale / Q000737:chemistry*; D019073:HT29 Cells; D006722:Honey; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000235:genetics; D051058:Oncogene Protein v-akt / Q000235:genetics; D008517:Phytotherapy / Q000379:methods*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D028321:Plant Preparations / Q000737:chemistry / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D017027:Protein Tyrosine Phosphatases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D016896:Treatment Outcome; D015854:Up-Regulation / Q000187:drug effects; D051020:bcl-X Protein / Q000235:genetics; D018631:ras Proteins / Q000235:genetics; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D000970:Antineoplastic Agents; D053453:Caspase 9; D051058:Oncogene Protein v-akt; D010936:Plant Extracts; D028321:Plant Preparations; D017346:Protein Serine-Threonine Kinases; D017027:Protein Tyrosine Phosphatases; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D051020:bcl-X Protein; D018631:ras Proteins; D000097782:NF-kappaB-Inducing Kinase; C494811:BCL2L1 protein, human; C117307:KRAS protein, human; C096335:B59 protein, human