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Clin Ter. 2015 Nov-Dec;166(6):e365-73. doi: 10.7417/T.2015.1902.

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.

Author information

1
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.

Abstract

BACKGROUND AND OBJECTIVES:

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.

MATERIALS AND 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.

KEYWORDS:

Cellular senescence; Genes expression; Senescence-associated signalling pathways; Tocotrienol-rich fraction

PMID:
26794818
DOI:
10.7417/T.2015.1902
[Indexed for MEDLINE]
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