Tocotrienol-rich fraction prevents cellular aging by modulating cell proliferation signaling pathways

S. C. Khor, Yasmin Anum Mohd Yusof, W. Z. Wan Ngah, Suzana Makpol

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

BACKGROUND AND OBJECTIVE: Vitamin E has been suggested as nutritional intervention for the prevention of degenerative and age-related diseases. In this study, we aimed to elucidate the underlying mechanism of tocotrienol-rich fraction (TRF) in delaying cellular aging by targeting the proliferation signaling pathways in human diploid fibroblasts (HDFs).

MATERIALS AND METHODS: Tocotrienol-rich fraction was used to treat different stages of cellular aging of primary human diploid fibroblasts viz. young (passage 6), pre-senescent (passage 15) and senescent (passage 30). Several selected targets involved in the downstream of PI3K/AKT and RAF/MEK/ERK pathways were compared in total RNA and protein.

RESULTS: Different transcriptional profiles were observed in young, pre-senescent and senescent HDFs, in which cellular aging increased AKT, FOXO3, CDKN1A and RSK1 mRNA expression level, but decreased ELK1, FOS and SIRT1 mRNA expression level. With tocotrienol-rich fraction treatment, gene expression of AKT, FOXO3, ERK and RSK1 mRNA was decreased in senescent cells, but not in young cells. The three down-regulated mRNA in cellular aging, ELK1, FOS and SIRT1, were increased with tocotrienol-rich fraction treatment. Expression of FOXO3 and P21Cip1 proteins showed up-regulation in senescent cells but tocotrienol-rich fraction only decreased P21Cip1 protein expression in senescent cells.

CONCLUSIONS: Tocotrienol-rich fraction exerts gene modulating properties that might be responsible in promoting cell cycle progression during cellular aging.

Original languageEnglish
Pages (from-to)e81-e90
JournalLa Clinica terapeutica
Volume166
Issue number2
DOIs
Publication statusPublished - 1 Jan 2015

Fingerprint

Tocotrienols
Cell Aging
Cell Proliferation
Diploidy
Messenger RNA
Fibroblasts
MAP Kinase Signaling System
Vitamin E
Phosphatidylinositol 3-Kinases
Cell Cycle
Proteins
Up-Regulation
RNA
Gene Expression
Genes

Keywords

  • Cellular aging
  • Gene expression
  • Human diploid fibroblasts
  • Tocotrienol-rich fraction
  • Vitamin E

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Tocotrienol-rich fraction prevents cellular aging by modulating cell proliferation signaling pathways. / Khor, S. C.; Mohd Yusof, Yasmin Anum; Wan Ngah, W. Z.; Makpol, Suzana.

In: La Clinica terapeutica, Vol. 166, No. 2, 01.01.2015, p. e81-e90.

Research output: Contribution to journalArticle

@article{ead1a6fde378430888d94e9fd8dd7349,
title = "Tocotrienol-rich fraction prevents cellular aging by modulating cell proliferation signaling pathways",
abstract = "BACKGROUND AND OBJECTIVE: Vitamin E has been suggested as nutritional intervention for the prevention of degenerative and age-related diseases. In this study, we aimed to elucidate the underlying mechanism of tocotrienol-rich fraction (TRF) in delaying cellular aging by targeting the proliferation signaling pathways in human diploid fibroblasts (HDFs).MATERIALS AND METHODS: Tocotrienol-rich fraction was used to treat different stages of cellular aging of primary human diploid fibroblasts viz. young (passage 6), pre-senescent (passage 15) and senescent (passage 30). Several selected targets involved in the downstream of PI3K/AKT and RAF/MEK/ERK pathways were compared in total RNA and protein.RESULTS: Different transcriptional profiles were observed in young, pre-senescent and senescent HDFs, in which cellular aging increased AKT, FOXO3, CDKN1A and RSK1 mRNA expression level, but decreased ELK1, FOS and SIRT1 mRNA expression level. With tocotrienol-rich fraction treatment, gene expression of AKT, FOXO3, ERK and RSK1 mRNA was decreased in senescent cells, but not in young cells. The three down-regulated mRNA in cellular aging, ELK1, FOS and SIRT1, were increased with tocotrienol-rich fraction treatment. Expression of FOXO3 and P21Cip1 proteins showed up-regulation in senescent cells but tocotrienol-rich fraction only decreased P21Cip1 protein expression in senescent cells.CONCLUSIONS: Tocotrienol-rich fraction exerts gene modulating properties that might be responsible in promoting cell cycle progression during cellular aging.",
keywords = "Cellular aging, Gene expression, Human diploid fibroblasts, Tocotrienol-rich fraction, Vitamin E",
author = "Khor, {S. C.} and {Mohd Yusof}, {Yasmin Anum} and {Wan Ngah}, {W. Z.} and Suzana Makpol",
year = "2015",
month = "1",
day = "1",
doi = "10.7417/T.2015.1825",
language = "English",
volume = "166",
pages = "e81--e90",
journal = "Clinica Terapeutica",
issn = "0009-9074",
publisher = "Societa Editrice Universo",
number = "2",

}

TY - JOUR

T1 - Tocotrienol-rich fraction prevents cellular aging by modulating cell proliferation signaling pathways

AU - Khor, S. C.

AU - Mohd Yusof, Yasmin Anum

AU - Wan Ngah, W. Z.

AU - Makpol, Suzana

PY - 2015/1/1

Y1 - 2015/1/1

N2 - BACKGROUND AND OBJECTIVE: Vitamin E has been suggested as nutritional intervention for the prevention of degenerative and age-related diseases. In this study, we aimed to elucidate the underlying mechanism of tocotrienol-rich fraction (TRF) in delaying cellular aging by targeting the proliferation signaling pathways in human diploid fibroblasts (HDFs).MATERIALS AND METHODS: Tocotrienol-rich fraction was used to treat different stages of cellular aging of primary human diploid fibroblasts viz. young (passage 6), pre-senescent (passage 15) and senescent (passage 30). Several selected targets involved in the downstream of PI3K/AKT and RAF/MEK/ERK pathways were compared in total RNA and protein.RESULTS: Different transcriptional profiles were observed in young, pre-senescent and senescent HDFs, in which cellular aging increased AKT, FOXO3, CDKN1A and RSK1 mRNA expression level, but decreased ELK1, FOS and SIRT1 mRNA expression level. With tocotrienol-rich fraction treatment, gene expression of AKT, FOXO3, ERK and RSK1 mRNA was decreased in senescent cells, but not in young cells. The three down-regulated mRNA in cellular aging, ELK1, FOS and SIRT1, were increased with tocotrienol-rich fraction treatment. Expression of FOXO3 and P21Cip1 proteins showed up-regulation in senescent cells but tocotrienol-rich fraction only decreased P21Cip1 protein expression in senescent cells.CONCLUSIONS: Tocotrienol-rich fraction exerts gene modulating properties that might be responsible in promoting cell cycle progression during cellular aging.

AB - BACKGROUND AND OBJECTIVE: Vitamin E has been suggested as nutritional intervention for the prevention of degenerative and age-related diseases. In this study, we aimed to elucidate the underlying mechanism of tocotrienol-rich fraction (TRF) in delaying cellular aging by targeting the proliferation signaling pathways in human diploid fibroblasts (HDFs).MATERIALS AND METHODS: Tocotrienol-rich fraction was used to treat different stages of cellular aging of primary human diploid fibroblasts viz. young (passage 6), pre-senescent (passage 15) and senescent (passage 30). Several selected targets involved in the downstream of PI3K/AKT and RAF/MEK/ERK pathways were compared in total RNA and protein.RESULTS: Different transcriptional profiles were observed in young, pre-senescent and senescent HDFs, in which cellular aging increased AKT, FOXO3, CDKN1A and RSK1 mRNA expression level, but decreased ELK1, FOS and SIRT1 mRNA expression level. With tocotrienol-rich fraction treatment, gene expression of AKT, FOXO3, ERK and RSK1 mRNA was decreased in senescent cells, but not in young cells. The three down-regulated mRNA in cellular aging, ELK1, FOS and SIRT1, were increased with tocotrienol-rich fraction treatment. Expression of FOXO3 and P21Cip1 proteins showed up-regulation in senescent cells but tocotrienol-rich fraction only decreased P21Cip1 protein expression in senescent cells.CONCLUSIONS: Tocotrienol-rich fraction exerts gene modulating properties that might be responsible in promoting cell cycle progression during cellular aging.

KW - Cellular aging

KW - Gene expression

KW - Human diploid fibroblasts

KW - Tocotrienol-rich fraction

KW - Vitamin E

UR - http://www.scopus.com/inward/record.url?scp=85016924953&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85016924953&partnerID=8YFLogxK

U2 - 10.7417/T.2015.1825

DO - 10.7417/T.2015.1825

M3 - Article

VL - 166

SP - e81-e90

JO - Clinica Terapeutica

JF - Clinica Terapeutica

SN - 0009-9074

IS - 2

ER -