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Inhibitory effect of temozolomide on apoptosis induction of cinnamaldehyde in human glioblastoma multiforme T98G cell line

  • Hedieh Abband (Department of Anatomy, Cellular and Molecular Research Center, School of Medicine, Guilan University of Medical Sciences) ;
  • Sara Dabirian (Department of Pharmaceutical Biotechnology, School of Pharmacy, Guilan University of Medical Sciences) ;
  • Adele Jafari (Department of Physiology, School of Medicine, Guilan University of Medical Sciences) ;
  • Mehran Nasiri (Department of Anatomy, Cellular and Molecular Research Center, School of Medicine, Guilan University of Medical Sciences) ;
  • Ebrahim Nasiri (Department of Anatomy, Cellular and Molecular Research Center, School of Medicine, Guilan University of Medical Sciences)
  • Received : 2023.06.05
  • Accepted : 2023.09.19
  • Published : 2024.03.31

Abstract

Glioblastoma is the most common primary malignant brain tumor in adults. Temozolomide (TMZ) is an FDA-approved drug used to treat this type of cancer. Cinnamaldehyde (CIN) is a derivative of cinnamon extract and makes up 99% of it. The aim of this study was to investigate the in vitro combined effect of CIN and TMZ on human glioblastoma multiforme T98G cell line viability. In this study, we used 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl-tertazolium bromide (MTT) method to evaluate the extent of IC50, acridine orange, Giemsa and Hoechst staining to evaluate the manner of apoptosis and the Western blotting method to examine the expression change of apoptotic proteins. Our results show that TMZ has an inhibitory effect on CIN when both used in combination at concentrations of 300 and 100 µM (P<0.05) and has a cytotoxic effect when used alone at the same concentrations (P<0.05). The western blotting result showed that TMZ at concentrations of 2,000 and 1,000 µM significantly increased Bax expression and decreased Bcl2 expression (P<0.05), indicating that TMZ induced apoptosis through the mitochondrial pathway. However, CIN had no effect on Bax and Bcl2 expressions, thus causing apoptosis from another pathway. Also, the Bax:Bcl2 expression ratio at concentrations combined was lower than that for TMZ 1,000 µM and higher than that for CIN 150 and 100 µM (P<0.05), which confirms the inhibitory effect of TMZ on CIN. From the present study, we conclude that TMZ in combination with CIN has an inhibitory effect on increasing the cytotoxicity rate.

Keywords

Acknowledgement

We greatly appreciate the support extended by Dr. Adele Jafari at Cellular and Molecular Research Center and Vice-Chancellor for Research of the Guilan University of Medical Sciences (IR.GUMS.REC.1394.233).

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