Benzyl isothiocyanate alters the gene expression with cell cycle regulation and cell death in human brain glioblastoma GBM 8401 cells

Tang,Nou-Ying; Chueh,Fu-Shin; Yu,Chien-Chih; Liao,Ching-Lung; Lin,Jen-Jyh; Hsia,Te-Chun; Wu,King-Chuen; Liu,Hsin-Chung; Lu,Kung-Wen; Chung,Jing-Gung

doi:10.3892/or.2016.4577

Benzyl isothiocyanate alters the gene expression with cell cycle regulation and cell death in human brain glioblastoma GBM 8401 cells

Authors:
- Nou-Ying Tang
- Fu-Shin Chueh
- Chien-Chih Yu
- Ching-Lung Liao
- Jen-Jyh Lin
- Te-Chun Hsia
- King-Chuen Wu
- Hsin-Chung Liu
- Kung-Wen Lu
- Jing-Gung Chung
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Affiliations: School of Chinese Medicine, China Medical University, Taichung 404, Taiwan, R.O.C., Department of Health and Nutrition Biotechnology, Asia University, Taichung 413, Taiwan, R.O.C., School of Pharmacy, China Medical University, Taichung 404, Taiwan, R.O.C., Division of Cardiology, China Medical University Hospital, Taichung 404, Taiwan, R.O.C., Department of Internal Medicine, China Medical University Hospital, Taichung 404, Taiwan, R.O.C., Department of Anesthesiology, E-Da Hospital/I-Shou University, Kaohsiung 824, Taiwan, R.O.C., Department of Biological Science and Technology, China Medical University, Taichung 404, Taiwan, R.O.C., School of Post-Baccalaureate Chinese Medicine, China Medical University, Taichung 404, Taiwan, R.O.C.
Published online on: January 19, 2016 https://doi.org/10.3892/or.2016.4577
Pages: 2089-2096

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Abstract

Glioblastoma multiforme (GBM) is a highly malignant devastating brain tumor in adults. Benzyl isothiocyanate (BITC) is one of the isothiocyanates that have been shown to induce human cancer cell apoptosis and cell cycle arrest. Herein, the effect of BITC on cell viability and apoptotic cell death and the genetic levels of human brain glioblastoma GBM 8401 cells in vitro were investigated. We found that BITC induced cell morphological changes, decreased cell viability and the induction of cell apoptosis in GBM 8401 cells was time-dependent. cDNA microarray was used to examine the effects of BITC on GBM 8401 cells and we found that numerous genes associated with cell death and cell cycle regulation in GBM 8401 cells were altered after BITC treatment. The results show that expression of 317 genes was upregulated, and two genes were associated with DNA damage, the DNA-damage-inducible transcript 3 (DDIT3) was increased 3.66-fold and the growth arrest and DNA-damage-inducible α (GADD45A) was increased 2.34-fold. We also found that expression of 182 genes was downregulated and two genes were associated with receptor for cell responses to stimuli, the EGF containing fibulin-like extracellular matrix protein 1 (EFEMP1) was inhibited 2.01-fold and the TNF receptor-associated protein 1 (TRAP1) was inhibited 2.08-fold. BITC inhibited seven mitochondria ribosomal genes, the mitochondrial ribosomal protein; tumor protein D52 (MRPS28) was inhibited 2.06-fold, the mitochondria ribosomal protein S2 (MRPS2) decreased 2.07-fold, the mitochondria ribosomal protein L23 (MRPL23) decreased 2.08-fold, the mitochondria ribosomal protein S2 (MRPS2) decreased 2.07-fold, the mitochondria ribosomal protein S12 (MRPS12) decreased 2.08-fold, the mitochondria ribosomal protein L12 (MRPL12) decreased 2.25-fold and the mitochondria ribosomal protein S34 (MRPS34) was decreased 2.30-fold in GBM 8401 cells. These changes of gene expression can provide the effects of BITC on the genetic level and are potential biomarkers for glioblastoma therapy.

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