期刊
ONCOTARGET
卷 6, 期 23, 页码 19580-19591出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.3973
关键词
thymoquinone; cancer metastasis; TWIST1; epithelial to mesenchymal transition; DNA methylation
资金
- National Natural Science Foundation of China [30371493, 81172049]
- Science and Technology Innovation Team of Colleges and Universities of Sichuan Province [13TD0032]
- Health Department Foundation of Sichuan Province [130261]
- Research Foundation of the Science and Technology Department of Sichuan Province [14JC0797, 2015JY0038]
- Luzhou City Special Foundation [2013LZLY-J10]
- Sichuan Medical University [20130512, 20130513]
Proteins that promote epithelial to mesenchymal transition (EMT) are associated with cancer metastasis. Inhibition of EMT regulators may be a promising approach in cancer therapy. In this study, Thymoquinone (TQ) was used to treat cancer cell lines to investigate its effects on EMT-regulatory proteins and cancer metastasis. We show that TQ inhibited cancer cell growth, migration and invasion in a dose-dependent manner. At the molecular level, TQ treatment decreased the transcriptional activity of the TWIST1 promoter and the mRNA expression of TWIST1, an EMT-promoting transcription factor. Accordingly, TQ treatment also decreased the expression of TWIST1-upregulated genes such as N-Cadherin and increased the expression of TWIST1-repressed genes such as E-Cadherin, resulting in a reduction of cell migration and invasion. TQ treatment also inhibited the growth and metastasis of cancer cell-derived xenograft tumors in mice but partially attenuated the migration and invasion in TWIST1-overexpressed cell lines. Furthermore, we found that TQ treatment enhanced the promoter DNA methylation of the TWIST1 gene in BT 549 cells. Together, these results demonstrate that TQ treatment inhibits TWIST1 promoter activity and decreases its expression, leading to the inhibition of cancer cell migration, invasion and metastasis. These findings suggest TQ as a potential small molecular inhibitor of cancer growth and metastasis.
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