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Resveratrol and siRNA in combination reduces Hsp27 expression and induces caspase-3 activity in human glioblastoma cells

  • Evren Önay UçarEmail author
  • Aslıhan Şengelen
Original Paper
  • 34 Downloads

Abstract

GBM cells can easily gain resistance to conventional therapy, and therefore treatment of glioblastoma multiforme (GBM) is difficult. One of the hallmark proteins known to be responsible for this resistance is heat shock protein 27 (Hsp27) which has a key role in the cell survival. Resveratrol, a natural compound, exhibits antitumor effects against GBM, but there are no reports regarding its effect on Hsp27 expression in gliomas. The aim of the present study was to asses the effect of resveratrol on Hsp27 expression and apoptosis in non-transfected and transfected U-87 MG human glioblastoma cells. In order to block the Hsp27 expression, siRNA transfection was performed. Non-transfected and transfected cells were treated with either 10 or 15 μM resveratrol. The effects of resveratrol were compared with quercetin, a well-known Hsp27 inhibitor. Resveratrol was found to induce apoptosis more effectively than quercetin. Our data showed that resveratrol induces dose- and time-dependent cell death. We also determined that silencing of Hsp27 with siRNA makes the cells more vulnerable to apoptosis upon resveratrol treatment. The highest effect was observed in the 15 μM resveratrol and 25 nM siRNA combination group (suppressed Hsp27 expression by 93.4% and induced apoptosis by 101.2%). This study is the first report showing that resveratrol reduces Hsp27 levels, and siRNA-mediated Hsp27 silencing enhances the therapeutic effects of resveratrol in glioma cells. Our results suggest that resveratrol administration in combination with Hsp27 silencing has a potential to be used as a candidate for GBM treatment.

Keywords

Resveratrol siRNA Combined therapy Hsp27 Glioma Apoptosis 

Abbreviations

AKT

Protein kinase B (PKB)

DMSO

Dimethyl sulfoxide

ER

Endoplasmic reticulum

GAPDH

Glyceraldehyde 3-phosphate dehydrogenase

GBM

Glioblastoma multiforme

HSF

Heat shock factor

Hsp

Heat shock protein

IC50

The half-maximal inhibitory concentration

MAPK

Mitogen-activated protein kinase

mTOR

Mammalian target of rapamycin

MTT

3-(4,5-Dimethylthiazol-2-yl) 2, 5-diphenyl-tetrazolium bromide

NF-κB

Nuclear factor kappa B

PI3K

Phosphatidylinositol 3-kinase

RNAi

RNA interference

siRNA

Small interfering RNA

Sirtuin 1

SIRT1

TNF-α

Tumor necrosis factor alpha

TRAIL

TNF-related apoptosis-inducing ligand

Notes

Funding information

This work was supported by the Istanbul University Research Foundation, Turkey (Project numbers 57959 and BEK-24987).

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Copyright information

© Cell Stress Society International 2019

Authors and Affiliations

  1. 1.Department of Molecular Biology and Genetics, Faculty of ScienceIstanbul UniversityIstanbulTurkey
  2. 2.Department of Molecular Biology and Genetics, Institute of Graduate Studies in SciencesIstanbul UniversityIstanbulTurkey

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