Suppression of phorbol-12-myristate-13-acetate-induced tumor cell invasion by apigenin via the inhibition of p38 mitogen-activated protein kinase-dependent matrix metalloproteinase-9 expression

Title
Suppression of phorbol-12-myristate-13-acetate-induced tumor cell invasion by apigenin via the inhibition of p38 mitogen-activated protein kinase-dependent matrix metalloproteinase-9 expression
Author(s)
송인환이태진김주영성언기노효정
Keywords
IV COLLAGENASE; MATRIX METALLOPROTEINASES; COLORECTAL-CANCER; EPITHELIAL-CELLS; BREAST-CANCER; METASTASIS; GROWTH; PROGELATINASE; ANTHOCYANINS; INVASIVENESS
Issue Date
201007
Publisher
SPANDIDOS PUBL LTD
Citation
ONCOLOGY REPORTS, v.24, no.1, pp.277 - 283
Abstract
Apigenin has special interest for the development of chemopreventive agents against cancer because it is a widely distributed plant flavonoid that has antitumor properties. In this study, we investigated the apigenin effects on the protease-mediated invasiveness in human metastatic cancer cell lines Caski, SK-Hep1 and MDA-231. We found that apigenin markedly inhibits the phorbol-12-myristate-13-acetate (PMA)-induced increase in MMP-9 expression and activity in several cancer cell lines. These effects of apigenin are close-dependent and correlate with the suppression of MMP-9 mRNA expression levels. PMA caused about a 5-fold induction in MMP-9 promoter activity, which was also suppressed by apigenin treatment in Caski cells. We found that apigenin could inhibit PMA-induced phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK), which was involved in the down-regulation of the expression of matrix metalloproteinase-9 (MMP-9) at mRNA levels. Furthermore, the treatment of inhibitors specific for p38 MAPK (SB203580) to Caski cells caused the reduction of MMP-9 expression. Restoration of p38 expression partly increased PMA-induced MMP-9 secretion blocked by apigenin treatment in Caski cells. These results showed apigenin might inhibit the invasion and migration abilities of Caski cells by reducing the MMP-9 expression through suppressing the p38 MAPK signaling pathway. These findings indicate that apigenin might be a useful strategy for controlling metastasis and the invasiveness of tumors.
URI
http://hdl.handle.net/YU.REPOSITORY/23950http://dx.doi.org/10.3892/or_00000857
ISSN
1021-335X
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의과대학 > 해부학교실 > Articles
의과대학 > 영상의학과학교실 > Articles
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