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Diallyl disulfide suppresses epithelial-mesenchymal transition, invasion and
proliferation by downregulation of LIMK1 in gastric cancer
#MMPMID26871290
Su B
; Su J
; Zeng Y
; Liu F
; Xia H
; Ma YH
; Zhou ZG
; Zhang S
; Yang BM
; Wu YH
; Zeng X
; Ai XH
; Ling H
; Jiang H
; Su Q
Oncotarget
2016[Mar]; 7
(9
): 10498-512
PMID26871290
show ga
Diallyl disulfide (DADS) has been shown to have multi-targeted antitumor
activities. We have previously discovered that it has a repressive effect on LIM
kinase-1 (LIMK1) expression in gastric cancer MGC803 cells. This suggests that
DADS may inhibit epithelial-mesenchymal transition (EMT) by downregulating LIMK1,
resulting in the inhibition of invasion and growth in gastric cancer. In this
study, we reveal that LIMK1 expression is correlated with tumor differentiation,
invasion depth, clinical stage, lymph node metastasis, and poor prognosis. DADS
downregulated the Rac1-Pak1/Rock1-LIMK1 pathway in MGC803 cells, as shown by
decreased p-LIMK1 and p-cofilin1 levels, and suppressed cell migration and
invasion. Knockdown and overexpression experiments performed in vitro
demonstrated that downregulating LIMK1 with DADS resulted in restrained EMT that
was coupled with decreased matrix metalloproteinase-9 (MMP-9) and increased
tissue inhibitor of metalloproteinase-3 (TIMP-3) expression. In in vitro and in
vivo experiments, the DADS-induced suppression of cell proliferation was enhanced
and antagonized by the knockdown and overexpression of LIMK1, respectively.
Similar results were observed for DADS-induced changes in the expression of
vimentin, CD34, Ki-67, and E-cadherin in xenografted tumors. These results
indicate that downregulation of LIMK1 by DADS could explain the inhibition of
EMT, invasion and proliferation in gastric cancer cells.
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