title: Targeting genes in insulin-associated signalling pathway, DNA damage, cell proliferation and cell differentiation pathways by tocotrienol-rich fraction in preventing cellular senescence of human diploid fibroblasts.
abstract: OBJECTIVE
  Tocotrienols have been known for their antioxidant properties besides their roles in cellular signalling, gene expression, immune response and apoptosis. This study aimed to determine the molecular mechanism of tocotrienol-rich fraction (TRF) in preventing cellular senescence of human diploid fibroblasts (HDFs) by targeting the genes in senescence-associated signalling pathways.
  
  
  METHODS
  Real time quantitative PCR (qRT-PCR) was utilized to evaluate the expression of genes involved in these pathways.
  
  
  RESULTS
  Our findings showed that SOD1 and CCS-1 were significantly down-regulated in pre-senescent cells while CCS-1 and PRDX6 were up-regulated in senescent cells (p<0.05). Treatment with TRF significantly down-regulated SOD1 in pre-senescent and senescent HDFs, up-regulated SOD2 in senescent cells, CAT in young HDFs, GPX1 in young and pre-senescent HDFs, and CCS-1 in young, pre-senescent and senescent HDFs (p<0.05). TRF treatment also caused up-regulation of FOXO3A in all age groups of cells (p<0.05). The expression of TP53, PAK2 and CDKN2A was significantly increased in senescent HDFs and treatment with TRF significantly down-regulated TP53 in senescent cells (p<0.05). MAPK14 was significantly up-regulated (p<0.05) in senescent HDFs while no changes was observed on the expression of JUN. TRF treatment, however, down-regulated MAPK14 in young and senescent cells and up-regulated JUN in young and pre-senescent HDFs (p<0.05).
  
  
  CONCLUSIONS
  TRF modulated the expression of genes involved in senescence-associated signalling pathways during replicative senescence of HDFs.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Level 17, Preclinical Building, Hospital Canselor Tuanku Muhriz, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia.
authors.forename: L W
authors.initials: LW
authors.lastname: Durani
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Level 17, Preclinical Building, Hospital Canselor Tuanku Muhriz, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia.
authors.forename: F
authors.initials: F
authors.lastname: Jaafar
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Level 17, Preclinical Building, Hospital Canselor Tuanku Muhriz, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia.
authors.forename: J K
authors.initials: JK
authors.lastname: Tan
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Level 17, Preclinical Building, Hospital Canselor Tuanku Muhriz, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia.
authors.forename: K
authors.initials: K
authors.lastname: Tajul Arifin
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Level 17, Preclinical Building, Hospital Canselor Tuanku Muhriz, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia.
authors.forename: Y A
authors.initials: YA
authors.lastname: Mohd Yusof
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Level 17, Preclinical Building, Hospital Canselor Tuanku Muhriz, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia.
authors.forename: W Z
authors.initials: WZ
authors.lastname: Wan Ngah
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Level 17, Preclinical Building, Hospital Canselor Tuanku Muhriz, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia.
authors.forename: S
authors.initials: S
authors.lastname: Makpol
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects* / Q000235:genetics; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D004249:DNA Damage / Q000187:drug effects*; D004171:Diploidy; D015536:Down-Regulation / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects* / Q000502:physiology; D005819:Genetic Markers; D006801:Humans; D061385:Insulins / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D024508:Tocotrienols / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000975:Antioxidants; D005819:Genetic Markers; D061385:Insulins; D024508:Tocotrienols
keywords: Cellular senescence; Genes expression; Senescence-associated signalling pathways; Tocotrienol-rich fraction