γ-Tocotrienol prevents cell cycle arrest in aged human fibroblast cells through p16INK4a pathway

Azalina Zainuddin, Chua Kien Hui, Jen Kit Tan, Faizul Jaafar, Suzana Makpol

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Human diploid fibroblasts (HDFs) proliferation in culture has been used as a model of aging at the cellular level. Growth arrest is one of the most important mechanisms responsible for replicative senescence. Recent researches have been focusing on the function of vitamin E in modulating cellular signaling and gene expression. Therefore, the aim of this study was to elucidate the effect of palm γ-tocotrienol (vitamin E) in modulating cellular aging through p16INK4a pathway in HDF cells. Primary culture of senescent HDFs was incubated with 70 μM of palm γ-tocotrienol for 24 hours. Silencing of p16INK4a was carried out by siRNA transfection. RNA was extracted from the different treatment groups and gene expression analysis was carried out by real-time reverse transcription polymerase chain reaction. Proteins that were regulated by p16INK4a were determined by western blot technique. The finding of this study showed that p16INK4a mRNA was overexpressed in senescent HDFs, and hypophosphorylated-pRb and cyclin D1 protein expressions were increased (p < 0.05). However, downregulation of p16INK4a and hypophosphorylated-pRb and cyclin D1 protein expressions (p < 0.05) by γ-tocotrienol led to modulation of the cell cycle regulation during cellular aging. In conclusion, senescent HDFs showed change in biological process specifically in cell cycle regulation with elevated expression of genes and proteins which may contribute to cell cycle arrest. Palm γ-tocotrienol may delay cellular senescence of HDFs by regulating cell cycle through downregulation of p16INK4a and hypophosphorylated-pRb and cyclin D1 protein expressions.

Original languageEnglish
Pages (from-to)1-7
Number of pages7
JournalJournal of Physiology and Biochemistry
DOIs
Publication statusAccepted/In press - 14 Oct 2016

Fingerprint

Tocotrienols
Fibroblasts
Cell Cycle Checkpoints
Diploidy
Cell Aging
Cells
Cyclin D1
Cell Cycle
Aging of materials
Proteins
Vitamin E
Cell culture
Gene expression
Down-Regulation
Cell signaling
Biological Phenomena
Gene Expression
Polymerase chain reaction
Transcription
Small Interfering RNA

Keywords

  • Cell cycle aging
  • Gene and protein expression
  • p16
  • Tocotrienol

ASJC Scopus subject areas

  • Physiology
  • Biochemistry

Cite this

γ-Tocotrienol prevents cell cycle arrest in aged human fibroblast cells through p16INK4a pathway. / Zainuddin, Azalina; Kien Hui, Chua; Tan, Jen Kit; Jaafar, Faizul; Makpol, Suzana.

In: Journal of Physiology and Biochemistry, 14.10.2016, p. 1-7.

Research output: Contribution to journalArticle

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