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result sql = The mechanism of fucoidan-induced apoptosis in leukemic cells: involvement of ERK1/2, JNK, glutathione, and nitric oxide.
The mechanism of fucoidan-induced apoptosis in leukemic cells: involvement of ERK1/2, JNK, glutathione, and nitric oxide.
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char = l;code = 108
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char = a;code = 97
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char = n;code = 110
char = a;code = 97
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char = 1;code = 49
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char = 2;code = 50
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char = (;code = 40
char = E;code = 69
char = R;code = 82
char = K;code = 75
char = 1;code = 49
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char = 2;code = 50
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char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = J;code = 74
char = N;code = 78
char = K;code = 75
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
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char = i;code = 105
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char = a;code = 97
char = s;code = 115
char = e;code = 101
char = d;code = 100
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = f;code = 102
char = u;code = 117
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char = o;code = 111
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char = d;code = 100
char = a;code = 97
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char = t;code = 116
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = H;code = 72
char = L;code = 76
char = -;code = 45
char = 6;code = 54
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char = ;code = 32
char = N;code = 78
char = B;code = 66
char = 4;code = 52
char = ,;code = 44
char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = T;code = 84
char = H;code = 72
char = P;code = 80
char = -;code = 45
char = 1;code = 49
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char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
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char = ;code = 32
char = b;code = 98
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char = t;code = 116
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = t;code = 116
char = ;code = 32
char = K;code = 75
char = 5;code = 53
char = 6;code = 54
char = 2;code = 50
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
char = ;code = 32
char = E;code = 69
char = R;code = 82
char = K;code = 75
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char = 2;code = 50
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = c;code = 99
char = c;code = 99
char = u;code = 117
char = r;code = 114
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = l;code = 108
char = i;code = 105
char = e;code = 101
char = r;code = 114
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char = t;code = 116
char = i;code = 105
char = m;code = 109
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = J;code = 74
char = N;code = 78
char = K;code = 75
char = ;code = 32
char = a;code = 97
char = c;code = 99
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char = i;code = 105
char = v;code = 118
char = a;code = 97
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 = J;code = 74
char = N;code = 78
char = K;code = 75
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = b;code = 98
char = l;code = 108
char = o;code = 111
char = c;code = 99
char = k;code = 107
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = M;code = 77
char = E;code = 69
char = K;code = 75
char = 1;code = 49
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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 = 46
char = ;code = 32
char = I;code = 73
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = d;code = 100
char = d;code = 100
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = f;code = 102
char = u;code = 117
char = c;code = 99
char = o;code = 111
char = i;code = 105
char = d;code = 100
char = a;code = 97
char = n;code = 110
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char = i;code = 105
char = n;code = 110
char = d;code = 100
char = u;code = 117
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = p;code = 112
char = o;code = 111
char = p;code = 112
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char = o;code = 111
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char = i;code = 105
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
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 = e;code = 101
char = d;code = 100
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char = a;code = 97
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char = d;code = 100
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = g;code = 103
char = l;code = 108
char = u;code = 117
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = i;code = 105
char = o;code = 111
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char = e;code = 101
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = /;code = 47
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = L;code = 76
char = -;code = 45
char = N;code = 78
char = A;code = 65
char = M;code = 77
char = E;code = 69
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = f;code = 102
char = u;code = 117
char = c;code = 99
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char = a;code = 97
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char = d;code = 100
char = e;code = 101
char = c;code = 99
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char = a;code = 97
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char = e;code = 101
char = d;code = 100
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char = r;code = 114
char = a;code = 97
char = c;code = 99
char = e;code = 101
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char = l;code = 108
char = u;code = 117
char = l;code = 108
char = a;code = 97
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char = l;code = 108
char = u;code = 117
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = i;code = 105
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char = c;code = 99
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char = i;code = 105
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char = a;code = 97
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char = d;code = 100
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char = t;code = 116
char = r;code = 114
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char = x;code = 120
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = ;code = 32
char = (;code = 40
char = N;code = 78
char = O;code = 79
char = );code = 41
char = ;code = 32
char = p;code = 112
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char = o;code = 111
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = .;code = 46
char = ;code = 32
char = B;code = 66
char = u;code = 117
char = t;code = 116
char = h;code = 104
char = i;code = 105
char = o;code = 111
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char = n;code = 110
char = e;code = 101
char = -;code = 45
char = [;code = 91
char = R;code = 82
char = ,;code = 44
char = S;code = 83
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char = -;code = 45
char = s;code = 115
char = u;code = 117
char = l;code = 108
char = f;code = 102
char = o;code = 111
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char = m;code = 109
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char = e;code = 101
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = H;code = 72
char = L;code = 76
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char = 6;code = 54
char = 0;code = 48
char = ;code = 32
char = c;code = 99
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char = l;code = 108
char = l;code = 108
char = s;code = 115
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char = m;code = 109
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char = e;code = 101
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char = s;code = 115
char = e;code = 101
char = n;code = 110
char = s;code = 115
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char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
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char = t;code = 116
char = o;code = 111
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char = f;code = 102
char = u;code = 117
char = c;code = 99
char = o;code = 111
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char = d;code = 100
char = a;code = 97
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char = .;code = 46
char = ;code = 32
char = D;code = 68
char = e;code = 101
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char = l;code = 108
char = e;code = 101
char = t;code = 116
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 = M;code = 77
char = E;code = 69
char = K;code = 75
char = K;code = 75
char = 1;code = 49
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char = a;code = 97
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char = d;code = 100
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char = i;code = 105
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char = i;code = 105
char = b;code = 98
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char = o;code = 111
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char = ;code = 32
char = M;code = 77
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char = K;code = 75
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char = r;code = 114
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char = s;code = 115
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char = a;code = 97
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char = l;code = 108
char = u;code = 117
char = l;code = 108
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 = e;code = 101
char = d;code = 100
char = ;code = 32
char = N;code = 78
char = O;code = 79
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char = p;code = 112
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char = o;code = 111
char = d;code = 100
char = u;code = 117
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char = a;code = 97
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char = t;code = 116
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char = o;code = 111
char = n;code = 110
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = J;code = 74
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char = K;code = 75
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char = a;code = 97
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char = S;code = 83
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char = 6;code = 54
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char = 0;code = 48
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char = i;code = 105
char = b;code = 98
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char = N;code = 78
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char = p;code = 112
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char = e;code = 101
char = a;code = 97
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char = e;code = 101
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char = H;code = 72
char = L;code = 76
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char = 6;code = 54
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char = T;code = 84
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char = K;code = 75
char = K;code = 75
char = 1;code = 49
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char = 1;code = 49
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char = E;code = 69
char = R;code = 82
char = K;code = 75
char = 1;code = 49
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char = 2;code = 50
char = ,;code = 44
char = ;code = 32
char = a;code = 97
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char = J;code = 74
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char = K;code = 75
char = ,;code = 44
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char = d;code = 100
char = e;code = 101
char = p;code = 112
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char = p;code = 112
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result sql = Fucoidan, a sulfated polysaccharide in brown seaweed, has various biological activities including anti-tumor activity. We investigated the effects of fucoidan on the apoptosis of human promyeloid leukemic cells and fucoidan-mediated signaling pathways. Fucoidan induced apoptosis of HL-60, NB4, and THP-1 cells, but not K562 cells. Fucoidan treatment of HL-60 cells induced activation of caspases-8, -9, and -3, the cleavage of Bid, and changed mitochondrial membrane permeability. Fucoidan-induced apoptosis, cleavage of procaspases, and changes in the mitochondrial membrane permeability were efficiently blocked by depletion of mitogen-activated protein kinase (MAPK) kinase kinase 1 (MEKK1), and inhibitors of MAPK kinase 1 (MEK1) and c Jun NH2-terminal kinase (JNK). The phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and JNK was increased in fucoidan-treated HL-60, NB4, and THP-1 cells, but not K562 cells. ERK1/2 activation occurred at earlier times than JNK activation and JNK activation was blocked by MEK1 inhibitor. In addition, fucoidan-induced apoptosis was inhibited by addition of glutathione and/or L-NAME, and fucoidan decreased intracellular glutathione concentrations and stimulated nitric oxide (NO) production. Buthionine-[R,S]-sulfoximine rendered HL-60 cells more sensitive to fucoidan. Depletion of MEKK1 and inhibition of MEK1 restored the intracellular glutathione content and abrogated NO production, whereas inhibition of JNK activation by SP600125 restored intracellular glutathione content but failed to inhibit NO production in fucoidan-treated HL-60 cells. These results suggest that activation of MEKK1, MEK1, ERK1/2, and JNK, depletion of glutathione, and production of NO are important mediators in fucoidan-induced apoptosis of human leukemic cells.

Publication: Mol. Carcinog. 2010 Aug ;49(8)::771-82. :doi: 10.1002/mc.20654.
Publication Date: 2010 Aug
Study Author(s): Jin, Jun-O;Song, Min-Gyu;Kim, Young-Nam;Park, Joo-In;Kwak, Jong-Young;
Institution: Department of Biochemistry, School of Medicine and Medical Research Center for Cancer Molecular Therapy, Dong-A University, Busan 602-714, Korea.
Shortcut link to this study:
Fucoidan, a sulfated polysaccharide in brown seaweed, has various biological activities including anti-tumor activity. We investigated the effects of fucoidan on the apoptosis of human promyeloid leukemic cells and fucoidan-mediated signaling pathways. Fucoidan induced apoptosis of HL-60, NB4, and THP-1 cells, but not K562 cells. Fucoidan treatment of HL-60 cells induced activation of caspases-8, -9, and -3, the cleavage of Bid, and changed mitochondrial membrane permeability. Fucoidan-induced apoptosis, cleavage of procaspases, and changes in the mitochondrial membrane permeability were efficiently blocked by depletion of mitogen-activated protein kinase (MAPK) kinase kinase 1 (MEKK1), and inhibitors of MAPK kinase 1 (MEK1) and c Jun NH2-terminal kinase (JNK). The phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and JNK was increased in fucoidan-treated HL-60, NB4, and THP-1 cells, but not K562 cells. ERK1/2 activation occurred at earlier times than JNK activation and JNK activation was blocked by MEK1 inhibitor. In addition, fucoidan-induced apoptosis was inhibited by addition of glutathione and/or L-NAME, and fucoidan decreased intracellular glutathione concentrations and stimulated nitric oxide (NO) production. Buthionine-[R,S]-sulfoximine rendered HL-60 cells more sensitive to fucoidan. Depletion of MEKK1 and inhibition of MEK1 restored the intracellular glutathione content and abrogated NO production, whereas inhibition of JNK activation by SP600125 restored intracellular glutathione content but failed to inhibit NO production in fucoidan-treated HL-60 cells. These results suggest that activation of MEKK1, MEK1, ERK1/2, and JNK, depletion of glutathione, and production of NO are important mediators in fucoidan-induced apoptosis of human leukemic cells.
PMID: 20572161

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