|
|
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char = K;code = 75
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result sql = Kaempferol-induced growth inhibition and apoptosis in A549 lung cancer cells is mediated by activation of MEK-MAPK.
Kaempferol-induced growth inhibition and apoptosis in A549 lung cancer cells is mediated by activation of MEK-MAPK.char = A;code = 65
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char = L;code = 76
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char = e;code = 101
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result sql = A vast variety of naturally occurring substances have been shown to protect against experimental carcinogenesis and an increasing amount of evidence suggests that kaempferol may have cancer chemopreventative properties. However, the precise underlying protective mechanisms are poorly understood. To elucidate these mechanisms, we challenged human lung cancer cell line A549 with kaempferol and investigated its effects upon cellular growth and signal transduction pathways. Treatment of A549 cells with kaempferol resulted in a dose- and time-dependent reduction in cell viability and DNA synthesis with the rate of apoptosis equivalent to 0.9+/-0.5, 5.2+/-1.5, 16.8+/-2.0, 25.4+/-2.6, and 37.8+/-4.5% on treatment with 0, 17.5, 35.0, 52.5, and 70.0 microM kaempferol, respectively. Concomitantly, kaempferol treatments led to a 1.2-, 2.7-, 3.3-, and 3.4-fold increase in Bax. Similar elevations were also observed in Bad which increased 1.2-, 3.3-, 3.7-, and 4.7-fold, respectively, as compared to control. Bcl-2 and Bcl-xL expression were inhibited in a dose-dependent fashion. While the Akt-1 and phosphorylated Akt-1 were inhibited, the mitogen-activated protein kinase (MAPK) was activated upon kaempferol treatment. Kaempferol induced apoptosis was associated with the cleavage of caspase-7 and poly ADP-ribose polymerase (PARP). Inhibition of MEK1/2 but not PI-3 kinase blocked kaempferol-induced cleavage of caspase-7, PARP cleavage, and apoptosis. The results suggest that inactivation of Akt-1 and alteration of Bcl-2 family of proteins are not sufficient for kaempferol to induce apoptosis and activation of MEK-MAPK is a requirement for kaempferol-induced cell death machinery in A549 cells.
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result sql = Kaempferol-induced growth inhibition and apoptosis in A549 lung cancer cells is mediated by activation of MEK-MAPK.
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char = e;code = 101
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char = C;code = 67
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char = n;code = 110
char = c;code = 99
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char = t;code = 116
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char = e;code = 101
char = a;code = 97
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char = d;code = 100
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char = t;code = 116
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char = 3;code = 51
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char = a;code = 97
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char = 3;code = 51
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char = o;code = 111
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char = i;code = 105
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char = e;code = 101
char = a;code = 97
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char = B;code = 66
char = a;code = 97
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char = ;code = 32
char = S;code = 83
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char = i;code = 105
char = l;code = 108
char = a;code = 97
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char = e;code = 101
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char = a;code = 97
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char = e;code = 101
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char = a;code = 97
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char = s;code = 115
char = o;code = 111
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char = o;code = 111
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char = s;code = 115
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char = r;code = 114
char = v;code = 118
char = e;code = 101
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char = i;code = 105
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char = B;code = 66
char = a;code = 97
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char = ;code = 32
char = w;code = 119
char = h;code = 104
char = i;code = 105
char = c;code = 99
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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
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char = .;code = 46
char = 3;code = 51
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char = ,;code = 44
char = ;code = 32
char = 3;code = 51
char = .;code = 46
char = 7;code = 55
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char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = 4;code = 52
char = .;code = 46
char = 7;code = 55
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char = f;code = 102
char = o;code = 111
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char = d;code = 100
char = ,;code = 44
char = ;code = 32
char = r;code = 114
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char = s;code = 115
char = p;code = 112
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = y;code = 121
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = s;code = 115
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char = c;code = 99
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char = m;code = 109
char = p;code = 112
char = a;code = 97
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = o;code = 111
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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 = 46
char = ;code = 32
char = B;code = 66
char = c;code = 99
char = l;code = 108
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char = 2;code = 50
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char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = B;code = 66
char = c;code = 99
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char = x;code = 120
char = L;code = 76
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char = e;code = 101
char = x;code = 120
char = p;code = 112
char = r;code = 114
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char = s;code = 115
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
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char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
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char = a;code = 97
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char = o;code = 111
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char = d;code = 100
char = e;code = 101
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char = e;code = 101
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char = d;code = 100
char = e;code = 101
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char = t;code = 116
char = ;code = 32
char = f;code = 102
char = a;code = 97
char = s;code = 115
char = h;code = 104
char = i;code = 105
char = o;code = 111
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char = W;code = 87
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char = l;code = 108
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char = A;code = 65
char = k;code = 107
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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 = o;code = 111
char = s;code = 115
char = p;code = 112
char = h;code = 104
char = o;code = 111
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char = y;code = 121
char = l;code = 108
char = a;code = 97
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = A;code = 65
char = k;code = 107
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char = -;code = 45
char = 1;code = 49
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char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
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char = n;code = 110
char = h;code = 104
char = i;code = 105
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char = d;code = 100
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char = o;code = 111
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char = P;code = 80
char = K;code = 75
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char = w;code = 119
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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 = c;code = 99
char = a;code = 97
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char = p;code = 112
char = a;code = 97
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char = ;code = 32
char = p;code = 112
char = o;code = 111
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char = y;code = 121
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char = A;code = 65
char = D;code = 68
char = P;code = 80
char = -;code = 45
char = r;code = 114
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char = b;code = 98
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char = s;code = 115
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char = e;code = 101
char = r;code = 114
char = a;code = 97
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char = e;code = 101
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char = (;code = 40
char = P;code = 80
char = A;code = 65
char = R;code = 82
char = P;code = 80
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char = .;code = 46
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char = I;code = 73
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
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 = M;code = 77
char = E;code = 69
char = K;code = 75
char = 1;code = 49
char = /;code = 47
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char = b;code = 98
char = u;code = 117
char = t;code = 116
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char = o;code = 111
char = t;code = 116
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char = P;code = 80
char = I;code = 73
char = -;code = 45
char = 3;code = 51
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char = k;code = 107
char = i;code = 105
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char = a;code = 97
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char = p;code = 112
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char = A;code = 65
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char = B;code = 66
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char = i;code = 105
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char = o;code = 111
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char = ;code = 32
char = M;code = 77
char = E;code = 69
char = K;code = 75
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char = M;code = 77
char = A;code = 65
char = P;code = 80
char = K;code = 75
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char = i;code = 105
char = s;code = 115
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char = i;code = 105
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char = p;code = 112
char = f;code = 102
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char = u;code = 117
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char = l;code = 108
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char = d;code = 100
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result sql = A vast variety of naturally occurring substances have been shown to protect against experimental carcinogenesis and an increasing amount of evidence suggests that kaempferol may have cancer chemopreventative properties. However, the precise underlying protective mechanisms are poorly understood. To elucidate these mechanisms, we challenged human lung cancer cell line A549 with kaempferol and investigated its effects upon cellular growth and signal transduction pathways. Treatment of A549 cells with kaempferol resulted in a dose- and time-dependent reduction in cell viability and DNA synthesis with the rate of apoptosis equivalent to 0.9+/-0.5, 5.2+/-1.5, 16.8+/-2.0, 25.4+/-2.6, and 37.8+/-4.5% on treatment with 0, 17.5, 35.0, 52.5, and 70.0 microM kaempferol, respectively. Concomitantly, kaempferol treatments led to a 1.2-, 2.7-, 3.3-, and 3.4-fold increase in Bax. Similar elevations were also observed in Bad which increased 1.2-, 3.3-, 3.7-, and 4.7-fold, respectively, as compared to control. Bcl-2 and Bcl-xL expression were inhibited in a dose-dependent fashion. While the Akt-1 and phosphorylated Akt-1 were inhibited, the mitogen-activated protein kinase (MAPK) was activated upon kaempferol treatment. Kaempferol induced apoptosis was associated with the cleavage of caspase-7 and poly ADP-ribose polymerase (PARP). Inhibition of MEK1/2 but not PI-3 kinase blocked kaempferol-induced cleavage of caspase-7, PARP cleavage, and apoptosis. The results suggest that inactivation of Akt-1 and alteration of Bcl-2 family of proteins are not sufficient for kaempferol to induce apoptosis and activation of MEK-MAPK is a requirement for kaempferol-induced cell death machinery in A549 cells.
Publication: J. Cell. Physiol. 2003 Oct ;197(1)::110-21.
Publication Date: 2003 Oct
Study Author(s): Nguyen, T T T;Tran, E;Ong, C K;Lee, S K;Do, P T;Huynh, T T;Nguyen, T H;Lee, J J;Tan, Y;Ong, C S;Huynh, H;
Institution: Laboratory of Molecular Endocrinology, Division of Cellular and Molecular Research, National Cancer Centre of Singapore, Singapore.
Shortcut link to this study:
Publication Date: 2003 Oct
Study Author(s): Nguyen, T T T;Tran, E;Ong, C K;Lee, S K;Do, P T;Huynh, T T;Nguyen, T H;Lee, J J;Tan, Y;Ong, C S;Huynh, H;
Institution: Laboratory of Molecular Endocrinology, Division of Cellular and Molecular Research, National Cancer Centre of Singapore, Singapore.
Shortcut link to this study:
A vast variety of naturally occurring substances have been shown to protect against experimental carcinogenesis and an increasing amount of evidence suggests that kaempferol may have cancer chemopreventative properties. However, the precise underlying protective mechanisms are poorly understood. To elucidate these mechanisms, we challenged human lung cancer cell line A549 with kaempferol and investigated its effects upon cellular growth and signal transduction pathways. Treatment of A549 cells with kaempferol resulted in a dose- and time-dependent reduction in cell viability and DNA synthesis with the rate of apoptosis equivalent to 0.9+/-0.5, 5.2+/-1.5, 16.8+/-2.0, 25.4+/-2.6, and 37.8+/-4.5% on treatment with 0, 17.5, 35.0, 52.5, and 70.0 microM kaempferol, respectively. Concomitantly, kaempferol treatments led to a 1.2-, 2.7-, 3.3-, and 3.4-fold increase in Bax. Similar elevations were also observed in Bad which increased 1.2-, 3.3-, 3.7-, and 4.7-fold, respectively, as compared to control. Bcl-2 and Bcl-xL expression were inhibited in a dose-dependent fashion. While the Akt-1 and phosphorylated Akt-1 were inhibited, the mitogen-activated protein kinase (MAPK) was activated upon kaempferol treatment. Kaempferol induced apoptosis was associated with the cleavage of caspase-7 and poly ADP-ribose polymerase (PARP). Inhibition of MEK1/2 but not PI-3 kinase blocked kaempferol-induced cleavage of caspase-7, PARP cleavage, and apoptosis. The results suggest that inactivation of Akt-1 and alteration of Bcl-2 family of proteins are not sufficient for kaempferol to induce apoptosis and activation of MEK-MAPK is a requirement for kaempferol-induced cell death machinery in A549 cells.
PMID: 12942547
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