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

L. W. Durani, F. Jaafar, J. K. Tan, Khaizurin Ajul Arifin, Yasmin Anum Mohd Yusof, W. Z. Wan Ngah, Suzana Makpol

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background and 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. 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). Conclusion. TRF modulated the expression of genes involved in senescence-associated signalling pathways during replicative senescence of HDFs.

Original languageEnglish
Pages (from-to)365-373
Number of pages9
JournalClinica Terapeutica
Volume166
Issue number6
DOIs
Publication statusPublished - 2015

Fingerprint

Tocotrienols
Gene Targeting
Cell Aging
Diploidy
DNA Damage
Cell Differentiation
Fibroblasts
Cell Proliferation
Insulin
Mitogen-Activated Protein Kinase 14
Gene Expression
Therapeutics
Real-Time Polymerase Chain Reaction
Up-Regulation
Age Groups
Antioxidants
Apoptosis

Keywords

  • Cellular senescence
  • Genes expression
  • Senescence-associated signalling pathways
  • Tocotrienol-rich fractiontocopherols

ASJC Scopus subject areas

  • Medicine(all)

Cite this

@article{6c44df8810744c38aa1a43086c4cebb7,
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 = "Background and 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. 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). Conclusion. 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 fractiontocopherols",
author = "Durani, {L. W.} and F. Jaafar and Tan, {J. K.} and {Ajul Arifin}, Khaizurin and {Mohd Yusof}, {Yasmin Anum} and {Wan Ngah}, {W. Z.} and Suzana Makpol",
year = "2015",
doi = "10.7417/T.2015.1902",
language = "English",
volume = "166",
pages = "365--373",
journal = "Clinica Terapeutica",
issn = "0009-9074",
publisher = "Societa Editrice Universo",
number = "6",

}

TY - JOUR

T1 - 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

AU - Durani, L. W.

AU - Jaafar, F.

AU - Tan, J. K.

AU - Ajul Arifin, Khaizurin

AU - Mohd Yusof, Yasmin Anum

AU - Wan Ngah, W. Z.

AU - Makpol, Suzana

PY - 2015

Y1 - 2015

N2 - Background and 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. 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). Conclusion. TRF modulated the expression of genes involved in senescence-associated signalling pathways during replicative senescence of HDFs.

AB - Background and 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. 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). Conclusion. TRF modulated the expression of genes involved in senescence-associated signalling pathways during replicative senescence of HDFs.

KW - Cellular senescence

KW - Genes expression

KW - Senescence-associated signalling pathways

KW - Tocotrienol-rich fractiontocopherols

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