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Furan‐2‐yl‐3‐Pyridin‐2‐yl‐Propenone Inhibits Invasion of HT1080 Human Fibrosarcoma Cells through Inhibitory Actions on the Expression of MT1‐MMP and MMP‐9 and Activation of proMMP‐2
Author(s) -
Park Byung Chil,
Lee YoonSeok,
Ko Yu Jin,
Lee EungSeok,
Kim JungAe
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1191
Subject(s) - ht1080 , fibrosarcoma , chemistry , matrix metalloproteinase , transfection , cancer research , microbiology and biotechnology , downregulation and upregulation , biochemistry , biology , in vitro , gene , genetics
Previously, 1‐furan‐2‐yl‐3‐pyridin‐2‐yl‐propenone (FPP‐3), a synthetic dual inhibitor of cycloxygenase/5‐lipoxygenase, has shown to possess inhibitory activities against nuclear factor‐¥êB (NF‐¥êB) activation. The present study investigated anti‐metastatic and anti‐invasive actions of FPP‐3 by using HT1080 human fibrosarcoma cells. FPP‐3 significantly suppressed the 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA)‐induced activation of proMMP‐2 and ‐9, in a concentration dependent manner in HT1080 tumor cells. Membrane type‐1‐MMP (MT1‐MMP) is a crucial element in the process of pro‐MMP‐2 activation by forming trimolecular complex with tissue inhibitor of metalloproteinase‐2 (TIMP‐2). FPP‐3 significantly blocked MT1‐MMP expression in a dose‐dependent manner whereas TIMP‐2 expression was weakly blocked by FPP‐3. In addition, FPP‐3 also decreased the expression of MMP‐9 but not TIMP‐1. As it is known that MT1‐MMP and MMP‐9 expression is regulated by NF‐¥êB, the effect of FPP‐3 on MT1‐MMP and MMP‐9 expression is mediated through suppression of NF‐¥êB activity since FPP‐3 clearly inhibited the TPA‐stimulated NF‐¥êB activation in the cells transiently transfected with NF‐¥êB promoter‐luciferase reporter construct. Furthermore, FPP‐3 inhibited the invasion and migration of HT1080 cells. Taken together, these results suggest that FPP‐3 may be a valuable candidate as an anticancer agent having anti‐invasive and anti‐metastatic activities. (Supported by grant No. RTI04‐01‐04 from the Regional Technology Innovation Program of the Ministry of Commerce, Industry, and Energy)