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2015 ; 6
(23
): 19580-91
Nephropedia Template TP
gab.com Text
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English Wikipedia
Thymoquinone inhibits cancer metastasis by downregulating TWIST1 expression to
reduce epithelial to mesenchymal transition
#MMPMID26023736
Khan MA
; Tania M
; Wei C
; Mei Z
; Fu S
; Cheng J
; Xu J
; Fu J
Oncotarget
2015[Aug]; 6
(23
): 19580-91
PMID26023736
show ga
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.