char = R;code = 82
char = e;code = 101
char = s;code = 115
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
char = s;code = 115
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 = 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 = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = p;code = 112
char = o;code = 111
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = t;code = 116
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
char = ;code = 32
char = b;code = 98
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = v;code = 118
char = i;code = 105
char = a;code = 97
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = v;code = 118
char = o;code = 111
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = m;code = 109
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = i;code = 105
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 = 46
result sql = Resveratrol induces growth inhibition and apoptosis in metastatic breast cancer cells via de novo ceramide signaling.
Resveratrol induces growth inhibition and apoptosis in metastatic breast cancer cells via de novo ceramide signaling.
char = R;code = 82
char = e;code = 101
char = s;code = 115
char = v;code = 118
char = e;code = 101
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char = a;code = 97
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = ;code = 32
char = (;code = 40
char = 3;code = 51
char = ,;code = 44
char = 4;code = 52
char = ';code = 39
char = ,;code = 44
char = 5;code = 53
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char = a;code = 97
char = n;code = 110
char = s;code = 115
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char = t;code = 116
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char = h;code = 104
char = y;code = 121
char = d;code = 100
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char = y;code = 121
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char = );code = 41
char = ,;code = 44
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char = h;code = 104
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char = l;code = 108
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char = g;code = 103
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char = a;code = 97
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char = e;code = 101
char = s;code = 115
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char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = w;code = 119
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char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = e;code = 101
char = m;code = 109
char = e;code = 101
char = r;code = 114
char = g;code = 103
char = i;code = 105
char = n;code = 110
char = g;code = 103
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 = a;code = 97
char = t;code = 116
char = u;code = 117
char = r;code = 114
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = c;code = 99
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char = m;code = 109
char = p;code = 112
char = o;code = 111
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char = w;code = 119
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char = t;code = 116
char = h;code = 104
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = p;code = 112
char = e;code = 101
char = r;code = 114
char = t;code = 116
char = i;code = 105
char = e;code = 101
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = H;code = 72
char = e;code = 101
char = r;code = 114
char = e;code = 101
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char = w;code = 119
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = h;code = 104
char = o;code = 111
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char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
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char = r;code = 114
char = e;code = 101
char = s;code = 115
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = u;code = 117
char = c;code = 99
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 = 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 = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = p;code = 112
char = o;code = 111
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = M;code = 77
char = D;code = 68
char = A;code = 65
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char = M;code = 77
char = B;code = 66
char = -;code = 45
char = 2;code = 50
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char = ,;code = 44
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char = a;code = 97
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char = h;code = 104
char = i;code = 105
char = g;code = 103
char = h;code = 104
char = l;code = 108
char = y;code = 121
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 = v;code = 118
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = t;code = 116
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
char = ;code = 32
char = b;code = 98
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = c;code = 99
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char = l;code = 108
char = l;code = 108
char = ;code = 32
char = l;code = 108
char = i;code = 105
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char = ,;code = 44
char = ;code = 32
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char = c;code = 99
char = o;code = 111
char = n;code = 110
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = i;code = 105
char = t;code = 116
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = d;code = 100
char = r;code = 114
char = a;code = 97
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = e;code = 101
char = n;code = 110
char = d;code = 100
char = o;code = 111
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = o;code = 111
char = u;code = 117
char = s;code = 115
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 = ;code = 32
char = o;code = 111
char = f;code = 102
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 = 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
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char = /;code = 47
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char = r;code = 114
char = o;code = 111
char = a;code = 97
char = p;code = 112
char = o;code = 111
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = m;code = 109
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = .;code = 46
char = ;code = 32
char = W;code = 87
char = e;code = 101
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = u;code = 117
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = c;code = 99
char = u;code = 117
char = m;code = 109
char = u;code = 117
char = l;code = 108
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char = i;code = 105
char = o;code = 111
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char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = c;code = 99
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char = r;code = 114
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char = d;code = 100
char = e;code = 101
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char = d;code = 100
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char = e;code = 101
char = s;code = 115
char = ;code = 32
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char = r;code = 114
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char = m;code = 109
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char = b;code = 98
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char = h;code = 104
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = v;code = 118
char = o;code = 111
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = m;code = 109
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char = d;code = 100
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char = s;code = 115
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char = n;code = 110
char = d;code = 100
char = ;code = 32
char = s;code = 115
char = p;code = 112
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char = i;code = 105
char = n;code = 110
char = g;code = 103
char = o;code = 111
char = m;code = 109
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char = e;code = 101
char = l;code = 108
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char = s;code = 115
char = .;code = 46
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char = M;code = 77
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char = f;code = 102
char = i;code = 105
char = c;code = 99
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char = l;code = 108
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char = e;code = 101
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char = e;code = 101
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char = S;code = 83
char = P;code = 80
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char = a;code = 97
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result sql = Resveratrol (3,4',5-trans-trihydroxystilbene), a phytoalexin present in grapes and red wine, is emerging as a natural compound with potential anticancer properties. Here we show that resveratrol can induce growth inhibition and apoptosis in MDA-MB-231, a highly invasive and metastatic breast cancer cell line, in concomitance with a dramatic endogenous increase of growth inhibitory/proapoptotic ceramide. We found that accumulation of ceramide derives from both de novo ceramide synthesis and sphingomyelin hydrolysis. More specifically we demonstrated that ceramide accumulation induced by resveratrol can be traced to the activation of serine palmitoyltransferase (SPT), the key enzyme of de novo ceramide biosynthetic pathway, and neutral sphingomyelinase (nSMase), a main enzyme involved in the sphingomyelin/ceramide pathway. However, by using specific inhibitors of SPT, myriocin and L-cycloserine, and nSMase, gluthatione and manumycin, we found that only the SPT inhibitors could counteract the biological effects induced by resveratrol. Thus, resveratrol seems to exert its growth inhibitory/apoptotic effect on the metastatic breast cancer cell line MDA-MB-231 by activating the de novo ceramide synthesis pathway.

Publication: FASEB J. 2003 Dec ;17(15)::2339-41.
Publication Date: 2003 Dec
Study Author(s): Scarlatti, Francesca;Sala, Giusy;Somenzi, Giulia;Signorelli, Paola;Sacchi, Nicoletta;Ghidoni, Riccardo;
Institution: Laboratory of Biochemistry and Molecular Biology, San Paolo University Hospital, School of Medicine, University of Milan, 20142 Milan, Italy.
Shortcut link to this study:
Resveratrol (3,4',5-trans-trihydroxystilbene), a phytoalexin present in grapes and red wine, is emerging as a natural compound with potential anticancer properties. Here we show that resveratrol can induce growth inhibition and apoptosis in MDA-MB-231, a highly invasive and metastatic breast cancer cell line, in concomitance with a dramatic endogenous increase of growth inhibitory/proapoptotic ceramide. We found that accumulation of ceramide derives from both de novo ceramide synthesis and sphingomyelin hydrolysis. More specifically we demonstrated that ceramide accumulation induced by resveratrol can be traced to the activation of serine palmitoyltransferase (SPT), the key enzyme of de novo ceramide biosynthetic pathway, and neutral sphingomyelinase (nSMase), a main enzyme involved in the sphingomyelin/ceramide pathway. However, by using specific inhibitors of SPT, myriocin and L-cycloserine, and nSMase, gluthatione and manumycin, we found that only the SPT inhibitors could counteract the biological effects induced by resveratrol. Thus, resveratrol seems to exert its growth inhibitory/apoptotic effect on the metastatic breast cancer cell line MDA-MB-231 by activating the de novo ceramide synthesis pathway.
PMID: 14563682

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