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char = s;code = 115
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char = a;code = 97
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char = N;code = 78
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char = p;code = 112
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char = n;code = 110
char = d;code = 100
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char = P;code = 80
char = E;code = 69
char = I;code = 73
char = T;code = 84
char = C;code = 67
char = ;code = 32
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char = h;code = 104
char = r;code = 114
char = o;code = 111
char = u;code = 117
char = g;code = 103
char = h;code = 104
char = ;code = 32
char = I;code = 73
char = k;code = 107
char = a;code = 97
char = p;code = 112
char = p;code = 112
char = a;code = 97
char = B;code = 66
char = a;code = 97
char = l;code = 108
char = p;code = 112
char = h;code = 104
char = a;code = 97
char = ,;code = 44
char = ;code = 32
char = I;code = 73
char = K;code = 75
char = K;code = 75
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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
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = h;code = 104
char = u;code = 117
char = m;code = 109
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = p;code = 112
char = r;code = 114
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char = a;code = 97
char = t;code = 116
char = e;code = 101
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 = P;code = 80
char = C;code = 67
char = -;code = 45
char = 3;code = 51
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 = 46
result sql = Suppression of NF-kappaB and NF-kappaB-regulated gene expression by sulforaphane and PEITC through IkappaBalpha, IKK pathway in human prostate cancer PC-3 cells.
Suppression of NF-kappaB and NF-kappaB-regulated gene expression by sulforaphane and PEITC through IkappaBalpha, IKK pathway in human prostate cancer PC-3 cells.
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char = t;code = 116
char = u;code = 117
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char = c;code = 99
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char = ;code = 32
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char = a;code = 97
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char = s;code = 115
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char = C;code = 67
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char = s;code = 115
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char = p;code = 112
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char = B;code = 66
char = ;code = 32
char = (;code = 40
char = N;code = 78
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char = p;code = 112
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char = s;code = 115
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char = o;code = 111
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char = p;code = 112
char = a;code = 97
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char = a;code = 97
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char = ;code = 32
char = i;code = 105
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char = P;code = 80
char = C;code = 67
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char = 3;code = 51
char = ;code = 32
char = C;code = 67
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char = l;code = 108
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char = o;code = 111
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char = u;code = 117
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char = t;code = 116
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char = e;code = 101
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char = a;code = 97
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char = i;code = 105
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char = u;code = 117
char = t;code = 116
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char = t;code = 116
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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 = o;code = 111
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char = ;code = 32
char = N;code = 78
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char = k;code = 107
char = a;code = 97
char = p;code = 112
char = p;code = 112
char = a;code = 97
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char = a;code = 97
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char = a;code = 97
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char = k;code = 107
char = a;code = 97
char = p;code = 112
char = p;code = 112
char = a;code = 97
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char = a;code = 97
char = l;code = 108
char = p;code = 112
char = h;code = 104
char = a;code = 97
char = );code = 41
char = ;code = 32
char = (;code = 40
char = S;code = 83
char = R;code = 82
char = -;code = 45
char = I;code = 73
char = k;code = 107
char = a;code = 97
char = p;code = 112
char = p;code = 112
char = a;code = 97
char = B;code = 66
char = a;code = 97
char = l;code = 108
char = p;code = 112
char = h;code = 104
char = a;code = 97
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char = .;code = 46
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char = a;code = 97
char = l;code = 108
char = o;code = 111
char = g;code = 103
char = o;code = 111
char = u;code = 117
char = s;code = 115
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char = t;code = 116
char = o;code = 111
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = a;code = 97
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char = m;code = 109
char = e;code = 101
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char = t;code = 116
char = s;code = 115
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char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
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char = S;code = 83
char = F;code = 70
char = N;code = 78
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
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char = P;code = 80
char = E;code = 69
char = I;code = 73
char = T;code = 84
char = C;code = 67
char = ,;code = 44
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char = S;code = 83
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char = -;code = 45
char = I;code = 73
char = k;code = 107
char = a;code = 97
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char = p;code = 112
char = a;code = 97
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char = a;code = 97
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char = t;code = 116
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char = i;code = 105
char = b;code = 98
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char = k;code = 107
char = a;code = 97
char = p;code = 112
char = p;code = 112
char = a;code = 97
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char = c;code = 99
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char = t;code = 116
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char = a;code = 97
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char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
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char = t;code = 116
char = y;code = 121
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char = ;code = 32
char = w;code = 119
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = a;code = 97
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char = V;code = 86
char = E;code = 69
char = G;code = 71
char = F;code = 70
char = ,;code = 44
char = ;code = 32
char = c;code = 99
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char = l;code = 108
char = c;code = 99
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char = ;code = 32
char = a;code = 97
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char = B;code = 66
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char = L;code = 76
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char = s;code = 115
char = i;code = 105
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char = S;code = 83
char = F;code = 70
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char = ;code = 32
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char = P;code = 80
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char = I;code = 73
char = T;code = 84
char = C;code = 67
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char = U;code = 85
char = V;code = 86
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char = ;code = 32
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char = k;code = 107
char = a;code = 97
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char = p;code = 112
char = a;code = 97
char = B;code = 66
char = a;code = 97
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char = a;code = 97
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char = U;code = 85
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char = p;code = 112
char = a;code = 97
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char = h;code = 104
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char = s;code = 115
char = t;code = 116
char = r;code = 114
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char = a;code = 97
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char = g;code = 103
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char = a;code = 97
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char = a;code = 97
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char = a;code = 97
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char = I;code = 73
char = K;code = 75
char = K;code = 75
char = b;code = 98
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char = a;code = 97
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char = F;code = 70
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char = T;code = 84
char = C;code = 67
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char = p;code = 112
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char = ;code = 32
char = a;code = 97
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char = d;code = 100
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char = E;code = 69
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char = T;code = 84
char = C;code = 67
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char = I;code = 73
char = K;code = 75
char = K;code = 75
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char = t;code = 116
char = a;code = 97
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char = K;code = 75
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char = a;code = 97
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char = a;code = 97
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char = d;code = 100
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result sql = Recent studies indicate that natural isothiocyanates, such as sulforaphane (SFN) and phenethyl isothiocyanate (PEITC) possess strong antitumor activities in vitro and in vivo. The nuclear factor kappa B (NF-kappaB) is believed to play an important role in cancer chemoprevention due to its involvement in tumor cell growth, proliferation, angiogenesis, invasion, apoptosis, and survival. In this study, we investigated the effects and the molecular mechanisms of SFN and PEITC on NF-kappaB transcriptional activation and NF-kappaB-regulated gene expression in human prostate cancer PC-3 C4 cells. Treatment with SFN (20 and 30 microM) and PEITC (5 and 7.5 microM) significantly inhibited NF-kappaB transcriptional activity, nuclear transloction of p65, and gene expression of NF-kappaB-regulated VEGF, cylcin D1, and Bcl-X(L) in PC-3 C4 cells. To further elucidate the mechanism, we utilized the dominant-negative mutant of inhibitor of NF-kappaB alpha (IkappaBalpha) (SR-IkappaBalpha). Analogous to treatments with SFN and PEITC, SR-IkappaBalpha also strongly inhibited NF-kappaB transcriptional activity as well as VEGF, cylcin D1, and Bcl-X(L) expression. Furthermore, SFN and PEITC also inhibited the basal and UVC-induced phosphorylation of IkappaBalpha and blocked UVC-induced IkappaBalpha degradation in PC-3 C4 cells. In examining the upstream signaling, we found that the dominant-negative mutant of IKKbeta (dnIKKbeta) possessed inhibitory effects similar to SFN and PEITC on NF-kappaB, VEGF, cylcin D1, Bcl-X(L) as well as IkappaBalpha phosphorylation. In addition, treatment with SFN and PEITC potently inhibited phosphorylation of both IKKbeta and IKKalpha and significantly inhibited the in vitro phosphorylation of IkappaBalpha mediated by IKKbeta. Taken together, these results suggest that the inhibition of SFN and PEITC on NF-kappaB transcriptional activation as well as NF-kappaB-regulated VEGF, cyclin D1, and Bcl-X(L) gene expression is mainly mediated through the inhibition of IKK phosphorylation, particularly IKKbeta, and the inhibition of IkappaBalpha phosphorylation and degradation, as well as the decrease of nuclear translocation of p65 in PC-3 cells.

Publication: Oncogene 2005 Jun 30 ;24(28)::4486-95.
Publication Date: 2005 Jun 30
Study Author(s): Xu, Changjiang;Shen, Guoxiang;Chen, Chi;Gélinas, Céline;Kong, Ah-Ng Tony;
Institution: Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
Shortcut link to this study:
Recent studies indicate that natural isothiocyanates, such as sulforaphane (SFN) and phenethyl isothiocyanate (PEITC) possess strong antitumor activities in vitro and in vivo. The nuclear factor kappa B (NF-kappaB) is believed to play an important role in cancer chemoprevention due to its involvement in tumor cell growth, proliferation, angiogenesis, invasion, apoptosis, and survival. In this study, we investigated the effects and the molecular mechanisms of SFN and PEITC on NF-kappaB transcriptional activation and NF-kappaB-regulated gene expression in human prostate cancer PC-3 C4 cells. Treatment with SFN (20 and 30 microM) and PEITC (5 and 7.5 microM) significantly inhibited NF-kappaB transcriptional activity, nuclear transloction of p65, and gene expression of NF-kappaB-regulated VEGF, cylcin D1, and Bcl-X(L) in PC-3 C4 cells. To further elucidate the mechanism, we utilized the dominant-negative mutant of inhibitor of NF-kappaB alpha (IkappaBalpha) (SR-IkappaBalpha). Analogous to treatments with SFN and PEITC, SR-IkappaBalpha also strongly inhibited NF-kappaB transcriptional activity as well as VEGF, cylcin D1, and Bcl-X(L) expression. Furthermore, SFN and PEITC also inhibited the basal and UVC-induced phosphorylation of IkappaBalpha and blocked UVC-induced IkappaBalpha degradation in PC-3 C4 cells. In examining the upstream signaling, we found that the dominant-negative mutant of IKKbeta (dnIKKbeta) possessed inhibitory effects similar to SFN and PEITC on NF-kappaB, VEGF, cylcin D1, Bcl-X(L) as well as IkappaBalpha phosphorylation. In addition, treatment with SFN and PEITC potently inhibited phosphorylation of both IKKbeta and IKKalpha and significantly inhibited the in vitro phosphorylation of IkappaBalpha mediated by IKKbeta. Taken together, these results suggest that the inhibition of SFN and PEITC on NF-kappaB transcriptional activation as well as NF-kappaB-regulated VEGF, cyclin D1, and Bcl-X(L) gene expression is mainly mediated through the inhibition of IKK phosphorylation, particularly IKKbeta, and the inhibition of IkappaBalpha phosphorylation and degradation, as well as the decrease of nuclear translocation of p65 in PC-3 cells.
PMID: 15856023

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