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char = i;code = 105
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char = ;code = 32
char = f;code = 102
char = a;code = 97
char = t;code = 116
char = t;code = 116
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char = c;code = 99
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char = d;code = 100
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char = t;code = 116
char = h;code = 104
char = a;code = 97
char = s;code = 115
char = e;code = 101
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char = b;code = 98
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char = l;code = 108
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char = n;code = 110
char = ;code = 32
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char = o;code = 111
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char = t;code = 116
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char = t;code = 116
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char = n;code = 110
char = s;code = 115
char = c;code = 99
char = r;code = 114
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char = p;code = 112
char = t;code = 116
char = i;code = 105
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char = l;code = 108
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char = w;code = 119
char = n;code = 110
char = -;code = 45
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = s;code = 115
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char = c;code = 99
char = -;code = 45
char = M;code = 77
char = e;code = 101
char = t;code = 116
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = e;code = 101
char = p;code = 112
char = e;code = 101
char = n;code = 110
char = d;code = 100
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = o;code = 111
char = s;code = 115
char = o;code = 111
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = /;code = 47
char = l;code = 108
char = y;code = 121
char = s;code = 115
char = o;code = 111
char = s;code = 115
char = o;code = 111
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = g;code = 103
char = r;code = 114
char = a;code = 97
char = d;code = 100
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = .;code = 46
result sql = Inhibition of fatty acid synthase by luteolin post-transcriptionally down-regulates c-Met expression independent of proteosomal/lysosomal degradation.
Inhibition of fatty acid synthase by luteolin post-transcriptionally down-regulates c-Met expression independent of proteosomal/lysosomal degradation.
char = T;code = 84
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char = e;code = 101
char = ;code = 32
char = h;code = 104
char = e;code = 101
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char = a;code = 97
char = t;code = 116
char = o;code = 111
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = g;code = 103
char = r;code = 114
char = o;code = 111
char = w;code = 119
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = f;code = 102
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = (;code = 40
char = H;code = 72
char = G;code = 71
char = F;code = 70
char = );code = 41
char = /;code = 47
char = c;code = 99
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char = M;code = 77
char = e;code = 101
char = t;code = 116
char = ;code = 32
char = s;code = 115
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char = g;code = 103
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = w;code = 119
char = a;code = 97
char = y;code = 121
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = v;code = 118
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char = e;code = 101
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char = ;code = 32
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char = h;code = 104
char = e;code = 101
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char = g;code = 103
char = r;code = 114
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char = s;code = 115
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char = n;code = 110
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char = o;code = 111
char = f;code = 102
char = ;code = 32
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char = v;code = 118
char = e;code = 101
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char = a;code = 97
char = l;code = 108
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
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char = s;code = 115
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char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = a;code = 97
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char = s;code = 115
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char = a;code = 97
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = u;code = 117
char = m;code = 109
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = v;code = 118
char = a;code = 97
char = s;code = 115
char = i;code = 105
char = o;code = 111
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char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
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char = m;code = 109
char = e;code = 101
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char = a;code = 97
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = c;code = 99
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char = p;code = 112
char = o;code = 111
char = t;code = 116
char = e;code = 101
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char = i;code = 105
char = a;code = 97
char = l;code = 108
char = .;code = 46
char = ;code = 32
char = W;code = 87
char = e;code = 101
char = ;code = 32
char = d;code = 100
char = e;code = 101
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char = e;code = 101
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char = i;code = 105
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char = v;code = 118
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char = o;code = 111
char = u;code = 117
char = s;code = 115
char = l;code = 108
char = y;code = 121
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char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = p;code = 112
char = h;code = 104
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char = l;code = 108
char = ;code = 32
char = e;code = 101
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char = g;code = 103
char = a;code = 97
char = l;code = 108
char = l;code = 108
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char = c;code = 99
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char = l;code = 108
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char = p;code = 112
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char = f;code = 102
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char = c;code = 99
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char = l;code = 108
char = ;code = 32
char = l;code = 108
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char = e;code = 101
char = s;code = 115
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char = i;code = 105
char = n;code = 110
char = ;code = 32
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char = t;code = 116
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char = n;code = 110
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char = ;code = 32
char = l;code = 108
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char = p;code = 112
char = i;code = 105
char = d;code = 100
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char = a;code = 97
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char = a;code = 97
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char = t;code = 116
char = y;code = 121
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char = a;code = 97
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char = i;code = 105
char = d;code = 100
char = ;code = 32
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char = e;code = 101
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char = (;code = 40
char = F;code = 70
char = A;code = 65
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char = );code = 41
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = m;code = 109
char = p;code = 112
char = l;code = 108
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char = a;code = 97
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
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char = ;code = 32
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = c;code = 99
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char = r;code = 114
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char = a;code = 97
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char = e;code = 101
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char = a;code = 97
char = f;code = 102
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char = f;code = 102
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char = f;code = 102
char = e;code = 101
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char = ;code = 32
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char = ;code = 32
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char = i;code = 105
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char = e;code = 101
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char = ;code = 32
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char = e;code = 101
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char = c;code = 99
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char = v;code = 118
char = i;code = 105
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char = ;code = 32
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char = e;code = 101
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char = 6;code = 54
char = S;code = 83
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = o;code = 111
char = s;code = 115
char = o;code = 111
char = m;code = 109
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = i;code = 105
char = d;code = 100
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = l;code = 108
char = y;code = 121
char = s;code = 115
char = o;code = 111
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char = o;code = 111
char = m;code = 109
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char = ;code = 32
char = T;code = 84
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char = k;code = 107
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = o;code = 111
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char = e;code = 101
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = t;code = 116
char = u;code = 117
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char = w;code = 119
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char = ;code = 32
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char = ;code = 32
char = n;code = 110
char = o;code = 111
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char = e;code = 101
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char = ;code = 32
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char = n;code = 110
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char = c;code = 99
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char = o;code = 111
char = n;code = 110
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = w;code = 119
char = e;code = 101
char = e;code = 101
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char = ;code = 32
char = F;code = 70
char = A;code = 65
char = S;code = 83
char = N;code = 78
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = i;code = 105
char = t;code = 116
char = y;code = 121
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char = a;code = 97
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char = d;code = 100
char = ;code = 32
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char = e;code = 101
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char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
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char = o;code = 111
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char = g;code = 103
char = e;code = 101
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char = u;code = 117
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char = u;code = 117
char = l;code = 108
char = d;code = 100
char = ;code = 32
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char = c;code = 99
char = t;code = 116
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = ;code = 32
char = H;code = 72
char = G;code = 71
char = F;code = 70
char = /;code = 47
char = c;code = 99
char = -;code = 45
char = M;code = 77
char = e;code = 101
char = t;code = 116
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = c;code = 99
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = o;code = 111
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result sql = The hepatocyte growth factor (HGF)/c-Met signaling pathway is involved in the progression of several cancers and associated with increased tumor invasion and metastatic potential. We determined previously that the polyphenol epigallocatechin-3-gallate inhibited HGF-induced c-Met phosphorylation in a variety of tumor cell lines in part by disrupting lipid rafts. Fatty acid synthase (FASN) is implicated in cancer progression and may regulate lipid raft function. We therefore examined the effects of luteolin, a potent FASN inhibitor, on c-Met signaling. Luteolin blocked HGF-induced c-Met phosphorylation and scattering of DU145 prostate cancer cells, but inhibition required at least a 4 h preincubation time. Western blot analysis indicated that inhibition of HGF-induced scattering by luteolin occurred coincident with reduction of total c-Met protein in DU145 cells. In addition, luteolin-induced c-Met down-regulation was mimicked by a pharmacologic inhibitor of FASN, C75, or short hairpin RNA knockdown of FASN. Consistent with a role for FASN, loss of c-Met in cells treated with C75 or luteolin was prevented by exogenous addition of palmitate. Luteolin-induced loss of c-Met primarily occurred at a post-transcriptional level and involved cell surface internalization but did not involve translation inhibition, nor was it dependent on the activity of the 26S proteosome or acidic lysosomes. Taken together, our study shows a novel connection between FASN activity and c-Met protein expression and suggests that luteolin could act as a novel HGF/c-Met inhibitor by reducing expression of this receptor.

Publication: Mol. Cancer Ther. 2009 Jan ;8(1)::214-24. :doi: 10.1158/1535-7163.MCT-08-0722.
Publication Date: 2009 Jan
Study Author(s): Coleman, David T;Bigelow, Rebecca;Cardelli, James A;
Institution: Department of Microbiology and Immunology, Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130, USA.
Shortcut link to this study:
The hepatocyte growth factor (HGF)/c-Met signaling pathway is involved in the progression of several cancers and associated with increased tumor invasion and metastatic potential. We determined previously that the polyphenol epigallocatechin-3-gallate inhibited HGF-induced c-Met phosphorylation in a variety of tumor cell lines in part by disrupting lipid rafts. Fatty acid synthase (FASN) is implicated in cancer progression and may regulate lipid raft function. We therefore examined the effects of luteolin, a potent FASN inhibitor, on c-Met signaling. Luteolin blocked HGF-induced c-Met phosphorylation and scattering of DU145 prostate cancer cells, but inhibition required at least a 4 h preincubation time. Western blot analysis indicated that inhibition of HGF-induced scattering by luteolin occurred coincident with reduction of total c-Met protein in DU145 cells. In addition, luteolin-induced c-Met down-regulation was mimicked by a pharmacologic inhibitor of FASN, C75, or short hairpin RNA knockdown of FASN. Consistent with a role for FASN, loss of c-Met in cells treated with C75 or luteolin was prevented by exogenous addition of palmitate. Luteolin-induced loss of c-Met primarily occurred at a post-transcriptional level and involved cell surface internalization but did not involve translation inhibition, nor was it dependent on the activity of the 26S proteosome or acidic lysosomes. Taken together, our study shows a novel connection between FASN activity and c-Met protein expression and suggests that luteolin could act as a novel HGF/c-Met inhibitor by reducing expression of this receptor.
PMID: 19139131

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