title: Gelam honey attenuated radiation-induced cell death in human diploid fibroblasts by promoting cell cycle progression and inhibiting apoptosis.
abstract: BACKGROUND
  The interaction between ionizing radiation and substances in cells will induce the production of free radicals. These free radicals inflict damage to important biomolecules such as chromosomes, proteins and lipids which consequently trigger the expression of genes which are involved in protecting the cells or repair the oxidative damages. Honey has been known for its antioxidant properties and was used in medical and cosmetic products. Currently, research on honey is ongoing and diversifying. The aim of this study was to elucidate the role of Gelam honey as a radioprotector in human diploid fibroblast (HDFs) which were exposed to gamma-rays by determining the expression of genes and proteins involved in cell cycle regulation and cell death.
  
  
  METHODS
  Six groups of HDFs were studied viz. untreated control, irradiated HDFs, Gelam honey-treated HDFs and HDF treated with Gelam honey pre-, during- and post-irradiation. HDFs were treated with 6 mg/ml of sterilized Gelam honey (w/v) for 24 h and exposed to 1 Gray (Gy) of gamma-rays at the dose rate of 0.25 Gy/min.
  
  
  RESULTS
  Our findings showed that, gamma-irradiation at 1 Gy up-regulated ATM, p53, p16ink4a and cyclin D1 genes and subsequently initiated cell cycle arrest at G0/G1 phase and induced apoptosis (p < 0.05). Pre-treatment with Gelam honey however caused down regulation of these genes in irradiated HDFs while no significant changes was observed on the expression of GADD45 and PAK genes. The expression of ATM and p16 proteins was increased in irradiated HDFs but the p53 gene was translated into p73 protein which was also increased in irradiated HDFs. Gelam honey treatment however significantly decreased the expression of ATM, p73, and p16 proteins (p < 0.05) while the expression of cyclin D1 remained unchanged. Analysis on cell cycle profile showed that cells progressed to S phase with less percentage of cells in G0/G1 phase with Gelam honey treatment while apoptosis was inhibited.
  
  
  CONCLUSIONS
  Gelam honey acts a radioprotector against gamma-irradiation by attenuating radiation-induced cell death.
authors.forename: Tengku Ahbrizal Farizal
authors.initials: TA
authors.lastname: Tengku Ahmad
authors.forename: Faizul
authors.initials: F
authors.lastname: Jaafar
authors.forename: Zakiah
authors.initials: Z
authors.lastname: Jubri
authors.forename: Khairuddin
authors.initials: K
authors.lastname: Abdul Rahim
authors.forename: Nor Fadilah
authors.initials: NF
authors.lastname: Rajab
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, Malaysia. suzanamakpol@yahoo.com.
authors.forename: Suzana
authors.initials: S
authors.lastname: Makpol
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics / Q000528:radiation effects; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics / Q000378:metabolism; D001688:Biological Products / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects* / Q000235:genetics / Q000528:radiation effects; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004171:Diploidy; D015536:Down-Regulation; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D016193:G1 Phase; D005720:Gamma Rays; D015870:Gene Expression; D006722:Honey; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism; D016196:S Phase; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D000975:Antioxidants; D001688:Biological Products; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D019938:Cyclin D1; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins