|
|
char = G;code = 71
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char = a;code = 97
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char = k;code = 107
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char = a;code = 97
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char = e;code = 101
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char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
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char = e;code = 101
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char = t;code = 116
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char = e;code = 101
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char = e;code = 101
char = n;code = 110
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result sql = Glycogen synthase kinase 3beta regulates cell death induced by synthetic triterpenoids.
Glycogen synthase kinase 3beta regulates cell death induced by synthetic triterpenoids.char = T;code = 84
char = h;code = 104
char = e;code = 101
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char = o;code = 111
char = f;code = 102
char = ;code = 32
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char = r;code = 114
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char = r;code = 114
char = a;code = 97
char = m;code = 109
char = m;code = 109
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char = l;code = 108
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char = r;code = 114
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char = m;code = 109
char = a;code = 97
char = l;code = 108
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char = m;code = 109
char = a;code = 97
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char = e;code = 101
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char = c;code = 99
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char = l;code = 108
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char = b;code = 98
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char = l;code = 108
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char = b;code = 98
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char = a;code = 97
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char = a;code = 97
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char = a;code = 97
char = b;code = 98
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char = o;code = 111
char = o;code = 111
char = l;code = 108
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = s;code = 115
char = t;code = 116
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 = i;code = 105
char = n;code = 110
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
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char = a;code = 97
char = n;code = 110
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char = .;code = 46
char = ;code = 32
char = I;code = 73
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = i;code = 105
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char = w;code = 119
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char = k;code = 107
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = e;code = 101
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char = r;code = 114
char = e;code = 101
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char = ;code = 32
char = e;code = 101
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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 = C;code = 67
char = -;code = 45
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char = 8;code = 56
char = ;code = 32
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char = d;code = 100
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char = 2;code = 50
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char = a;code = 97
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char = 1;code = 49
char = ,;code = 44
char = 9;code = 57
char = (;code = 40
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char = 1;code = 49
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char = e;code = 101
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char = 2;code = 50
char = 8;code = 56
char = -;code = 45
char = o;code = 111
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = a;code = 97
char = c;code = 99
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char = d;code = 100
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char = (;code = 40
char = C;code = 67
char = D;code = 68
char = D;code = 68
char = O;code = 79
char = -;code = 45
char = M;code = 77
char = e;code = 101
char = );code = 41
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char = d;code = 100
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char = p;code = 112
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = i;code = 105
char = v;code = 118
char = e;code = 101
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
char = o;code = 111
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = c;code = 99
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char = c;code = 99
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char = c;code = 99
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char = l;code = 108
char = l;code = 108
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char = l;code = 108
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char = t;code = 116
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char = n;code = 110
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char = a;code = 97
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char = l;code = 108
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char = ;code = 32
char = m;code = 109
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char = c;code = 99
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char = m;code = 109
char = o;code = 111
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char = o;code = 111
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result sql = The induction of programmed cell death in premalignant or malignant cancer cells by chemopreventive agents could be a valuable tool to control prostate cancer initiation and progression. In this work, we present evidence that the C-28 methyl ester of the synthetic oleanane triterpenoid 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO-Me) induces cell death in androgen-responsive and unresponsive human prostate cancer cell lines at nanomolar and low micromolar concentrations. CDDO-Me induced caspase-3, caspase-8, and caspase-9 activation; poly(ADP-ribose) polymerase cleavage; internucleosomal DNA fragmentation; and loss of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction in PC3 and DU145 cells. However, caspase-3 and caspase-8 inhibition by Z-DEVD-fmk and Z-IETD-fmk, respectively, or general caspase inhibition by BOC-D-fmk or Z-VAD-fmk did not rescue loss of cell viability induced by CDDO-Me, suggesting the activation of additional caspase-independent mechanisms. Interestingly, CDDO-Me induced inactivating phosphorylation at Ser(9) of glycogen synthase kinase 3beta (GSK3beta), a multifunctional kinase that mediates essential events promoting prostate cancer development and acquisition of androgen independence. The GSK3 inhibitor lithium chloride and, more effectively, GSK3 gene silencing sensitized PC3 and DU145 prostate cancer cells to CDDO-Me cytotoxicity. These data suggest that modulation of GSK3beta activation is involved in the cell death pathway engaged by CDDO-Me in prostate cancer cells.
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result sql = Glycogen synthase kinase 3beta regulates cell death induced by synthetic triterpenoids.
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char = l;code = 108
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char = a;code = 97
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char = e;code = 101
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char = t;code = 116
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char = a;code = 97
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char = u;code = 117
char = a;code = 97
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char = l;code = 108
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char = o;code = 111
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char = t;code = 116
char = o;code = 111
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char = c;code = 99
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char = o;code = 111
char = l;code = 108
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char = r;code = 114
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 = a;code = 97
char = t;code = 116
char = i;code = 105
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char = p;code = 112
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char = r;code = 114
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char = s;code = 115
char = i;code = 105
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char = ;code = 32
char = I;code = 73
char = n;code = 110
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char = t;code = 116
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char = i;code = 105
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char = s;code = 115
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char = e;code = 101
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char = t;code = 116
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char = a;code = 97
char = t;code = 116
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char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = C;code = 67
char = -;code = 45
char = 2;code = 50
char = 8;code = 56
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char = m;code = 109
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char = s;code = 115
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
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char = e;code = 101
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char = s;code = 115
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char = e;code = 101
char = a;code = 97
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char = a;code = 97
char = n;code = 110
char = e;code = 101
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char = t;code = 116
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char = t;code = 116
char = e;code = 101
char = r;code = 114
char = p;code = 112
char = e;code = 101
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char = i;code = 105
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char = 2;code = 50
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char = c;code = 99
char = y;code = 121
char = a;code = 97
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char = 3;code = 51
char = ,;code = 44
char = 1;code = 49
char = 2;code = 50
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char = d;code = 100
char = i;code = 105
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char = l;code = 108
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char = a;code = 97
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char = a;code = 97
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char = 1;code = 49
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char = 9;code = 57
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char = 1;code = 49
char = 1;code = 49
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char = -;code = 45
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char = c;code = 99
char = ;code = 32
char = a;code = 97
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char = i;code = 105
char = d;code = 100
char = ;code = 32
char = (;code = 40
char = C;code = 67
char = D;code = 68
char = D;code = 68
char = O;code = 79
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char = M;code = 77
char = e;code = 101
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char = a;code = 97
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char = o;code = 111
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char = s;code = 115
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char = D;code = 68
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char = a;code = 97
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char = D;code = 68
char = N;code = 78
char = A;code = 65
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char = f;code = 102
char = r;code = 114
char = a;code = 97
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char = E;code = 69
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char = I;code = 73
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char = T;code = 84
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char = O;code = 79
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char = f;code = 102
char = m;code = 109
char = k;code = 107
char = ;code = 32
char = o;code = 111
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char = Z;code = 90
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char = V;code = 86
char = A;code = 65
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char = -;code = 45
char = f;code = 102
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char = C;code = 67
char = D;code = 68
char = D;code = 68
char = O;code = 79
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char = M;code = 77
char = e;code = 101
char = ,;code = 44
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result sql = The induction of programmed cell death in premalignant or malignant cancer cells by chemopreventive agents could be a valuable tool to control prostate cancer initiation and progression. In this work, we present evidence that the C-28 methyl ester of the synthetic oleanane triterpenoid 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO-Me) induces cell death in androgen-responsive and unresponsive human prostate cancer cell lines at nanomolar and low micromolar concentrations. CDDO-Me induced caspase-3, caspase-8, and caspase-9 activation; poly(ADP-ribose) polymerase cleavage; internucleosomal DNA fragmentation; and loss of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction in PC3 and DU145 cells. However, caspase-3 and caspase-8 inhibition by Z-DEVD-fmk and Z-IETD-fmk, respectively, or general caspase inhibition by BOC-D-fmk or Z-VAD-fmk did not rescue loss of cell viability induced by CDDO-Me, suggesting the activation of additional caspase-independent mechanisms. Interestingly, CDDO-Me induced inactivating phosphorylation at Ser(9) of glycogen synthase kinase 3beta (GSK3beta), a multifunctional kinase that mediates essential events promoting prostate cancer development and acquisition of androgen independence. The GSK3 inhibitor lithium chloride and, more effectively, GSK3 gene silencing sensitized PC3 and DU145 prostate cancer cells to CDDO-Me cytotoxicity. These data suggest that modulation of GSK3beta activation is involved in the cell death pathway engaged by CDDO-Me in prostate cancer cells.
Publication: Cancer Res. 2008 Sep 1 ;68(17)::6987-96. :doi: 10.1158/0008-5472.CAN-07-6362.
Publication Date: 2008 Sep 1
Study Author(s): Venè, Roberta;Larghero, Patrizia;Arena, Giuseppe;Sporn, Michael B;Albini, Adriana;Tosetti, Francesca;
Institution: Molecular Oncology and Angiogenesis Laboratory, Istituto Nazionale per la Ricerca sul Cancro (IST), Genova, Italy.
Shortcut link to this study:
Publication Date: 2008 Sep 1
Study Author(s): Venè, Roberta;Larghero, Patrizia;Arena, Giuseppe;Sporn, Michael B;Albini, Adriana;Tosetti, Francesca;
Institution: Molecular Oncology and Angiogenesis Laboratory, Istituto Nazionale per la Ricerca sul Cancro (IST), Genova, Italy.
Shortcut link to this study:
The induction of programmed cell death in premalignant or malignant cancer cells by chemopreventive agents could be a valuable tool to control prostate cancer initiation and progression. In this work, we present evidence that the C-28 methyl ester of the synthetic oleanane triterpenoid 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO-Me) induces cell death in androgen-responsive and unresponsive human prostate cancer cell lines at nanomolar and low micromolar concentrations. CDDO-Me induced caspase-3, caspase-8, and caspase-9 activation; poly(ADP-ribose) polymerase cleavage; internucleosomal DNA fragmentation; and loss of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction in PC3 and DU145 cells. However, caspase-3 and caspase-8 inhibition by Z-DEVD-fmk and Z-IETD-fmk, respectively, or general caspase inhibition by BOC-D-fmk or Z-VAD-fmk did not rescue loss of cell viability induced by CDDO-Me, suggesting the activation of additional caspase-independent mechanisms. Interestingly, CDDO-Me induced inactivating phosphorylation at Ser(9) of glycogen synthase kinase 3beta (GSK3beta), a multifunctional kinase that mediates essential events promoting prostate cancer development and acquisition of androgen independence. The GSK3 inhibitor lithium chloride and, more effectively, GSK3 gene silencing sensitized PC3 and DU145 prostate cancer cells to CDDO-Me cytotoxicity. These data suggest that modulation of GSK3beta activation is involved in the cell death pathway engaged by CDDO-Me in prostate cancer cells.
PMID: 18757413
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