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/;code = 47 char = o;code = 111 char = r;code = 114 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = p;code = 112 char = r;code = 114 char = e;code = 101 char = s;code = 115 char = e;code = 101 char = n;code = 110 char = c;code = 99 char = e;code = 101 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = s;code = 115 char = u;code = 117 char = n;code = 110 char = b;code = 98 char = u;code = 117 char = r;code = 114 char = n;code = 110 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 = A;code = 65 char = p;code = 112 char = i;code = 105 char = g;code = 103 char = e;code = 101 char = n;code = 110 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = t;code = 116 char = r;code = 114 char = e;code = 101 char = a;code = 97 char = t;code = 116 char = m;code = 109 char = e;code = 101 char = n;code = 110 char = t;code = 116 char = ;code = 32 char = e;code = 101 char = n;code = 110 char = h;code = 104 char = a;code = 97 char = n;code = 110 char = c;code = 99 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = U;code = 85 char = V;code = 86 char = B;code = 66 char = -;code = 45 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 = 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 = >;code = 62 char = 2;code = 50 char = -;code = 45 char = f;code = 102 char = o;code = 111 char = l;code = 108 char = d;code = 100 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = e;code = 101 char = a;code = 97 char = c;code = 99 char = h;code = 104 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = m;code = 109 char = o;code = 111 char = d;code = 100 char = e;code = 101 char = l;code = 108 char = s;code = 115 char = ;code = 32 char = t;code = 116 char = e;code = 101 char = s;code = 115 char = t;code = 116 char = e;code = 101 char = d;code = 100 char = .;code = 46 char = ;code = 32 char = W;code = 87 char = h;code = 104 char = e;code = 101 char = n;code = 110 char = ;code = 32 char = k;code = 107 char = e;code = 101 char = r;code = 114 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = n;code = 110 char = o;code = 111 char = c;code = 99 char = y;code = 121 char = t;code = 116 char = e;code = 101 char = s;code = 115 char = ;code = 32 char = w;code = 119 char = e;code = 101 char = r;code = 114 char = e;code = 101 char = ;code = 32 char = e;code = 101 char = x;code = 120 char = p;code = 112 char = o;code = 111 char = s;code = 115 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = t;code = 116 char = o;code = 111 char = ;code = 32 char = U;code = 85 char = V;code = 86 char = B;code = 66 char = ,;code = 44 char = ;code = 32 char = a;code = 97 char = p;code = 112 char = i;code = 105 char = g;code = 103 char = e;code = 101 char = n;code = 110 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = t;code = 116 char = r;code = 114 char = e;code = 101 char = a;code = 97 char = t;code = 116 char = m;code = 109 char = e;code = 101 char = n;code = 110 char = t;code = 116 char = ;code = 32 char = s;code = 115 char = t;code = 116 char = i;code = 105 char = m;code = 109 char = u;code = 117 char = l;code = 108 char = a;code = 97 char = t;code = 116 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = c;code = 99 char = h;code = 104 char = a;code = 97 char = n;code = 110 char = g;code = 103 char = e;code = 101 char = s;code = 115 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = B;code = 66 char = a;code = 97 char = x;code = 120 char = ;code = 32 char = l;code = 108 char = o;code = 111 char = c;code = 99 char = a;code = 97 char = l;code = 108 char = i;code = 105 char = z;code = 122 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 = 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 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = r;code = 114 char = e;code = 101 char = l;code = 108 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 = c;code = 99 char = y;code = 121 char = t;code = 116 char = o;code = 111 char = c;code = 99 char = h;code = 104 char = r;code = 114 char = o;code = 111 char = m;code = 109 char = e;code = 101 char = ;code = 32 char = c;code = 99 char = ;code = 32 char = f;code = 102 char = r;code = 114 char = o;code = 111 char = m;code = 109 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = m;code = 109 char = i;code = 105 char = t;code = 116 char = o;code = 111 char = c;code = 99 char = h;code = 104 char = o;code = 111 char = n;code = 110 char = d;code = 100 char = r;code = 114 char = i;code = 105 char = a;code = 97 char = ;code = 32 char = c;code = 99 char = o;code = 111 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 = w;code = 119 char = i;code = 105 char = t;code = 116 char = h;code = 104 char = ;code = 32 char = U;code = 85 char = V;code = 86 char = B;code = 66 char = ;code = 32 char = e;code = 101 char = x;code = 120 char = p;code = 112 char = o;code = 111 char = s;code = 115 char = u;code = 117 char = r;code = 114 char = e;code = 101 char = ;code = 32 char = a;code = 97 char = l;code = 108 char = o;code = 111 char = n;code = 110 char = e;code = 101 char = .;code = 46 char = ;code = 32 char = O;code = 79 char = v;code = 118 char = e;code = 101 char = r;code = 114 char = e;code = 101 char = x;code = 120 char = p;code = 112 char = r;code = 114 char = e;code = 101 char = s;code = 115 char = s;code = 115 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 = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = t;code = 116 char = i;code = 105 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 = p;code = 112 char = r;code = 114 char = o;code = 111 char = t;code = 116 char = e;code = 101 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = B;code = 66 char = c;code = 99 char = l;code = 108 char = -;code = 45 char = 2;code = 50 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = e;code = 101 char = x;code = 120 char = p;code = 112 char = r;code = 114 char = e;code = 101 char = s;code = 115 char = s;code = 115 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 = a;code = 97 char = ;code = 32 char = d;code = 100 char = o;code = 111 char = m;code = 109 char = i;code = 105 char = n;code = 110 char = a;code = 97 char = n;code = 110 char = t;code = 116 char = -;code = 45 char = n;code = 110 char = e;code = 101 char = g;code = 103 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = v;code = 118 char = e;code = 101 char = ;code = 32 char = f;code = 102 char = o;code = 111 char = r;code = 114 char = m;code = 109 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = F;code = 70 char = a;code = 97 char = s;code = 115 char = -;code = 45 char = a;code = 97 char = s;code = 115 char = s;code = 115 char = o;code = 111 char = c;code = 99 char = i;code = 105 char = a;code = 97 char = t;code = 116 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = d;code = 100 char = e;code = 101 char = a;code = 97 char = t;code = 116 char = h;code = 104 char = ;code = 32 char = d;code = 100 char = o;code = 111 char = m;code = 109 char = a;code = 97 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = l;code = 108 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = t;code = 116 char = o;code = 111 char = ;code = 32 char = a;code = 97 char = ;code = 32 char = r;code = 114 char = e;code = 101 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 = 32 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = a;code = 97 char = b;code = 98 char = i;code = 105 char = l;code = 108 char = i;code = 105 char = t;code = 116 char = y;code = 121 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = a;code = 97 char = p;code = 112 char = i;code = 105 char = g;code = 103 char = e;code = 101 char = n;code = 110 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = t;code = 116 char = o;code = 111 char = ;code = 32 char = e;code = 101 char = n;code = 110 char = h;code = 104 char = a;code = 97 char = n;code = 110 char = c;code = 99 char = e;code = 101 char = ;code = 32 char = U;code = 85 char = V;code = 86 char = B;code = 66 char = -;code = 45 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 = 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 = 46 char = ;code = 32 char = T;code = 84 char = h;code = 104 char = e;code = 101 char = s;code = 115 char = e;code = 101 char = ;code = 32 char = r;code = 114 char = e;code = 101 char = s;code = 115 char = u;code = 117 char = l;code = 108 char = t;code = 116 char = s;code = 115 char = ;code = 32 char = s;code = 115 char = u;code = 117 char = g;code = 103 char = g;code = 103 char = e;code = 101 char = s;code = 115 char = t;code = 116 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = a;code = 97 char = t;code = 116 char = ;code = 32 char = e;code = 101 char = n;code = 110 char = h;code = 104 char = a;code = 97 char = n;code = 110 char = c;code = 99 char = e;code = 101 char = m;code = 109 char = e;code = 101 char = n;code = 110 char = t;code = 116 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = U;code = 85 char = V;code = 86 char = B;code = 66 char = -;code = 45 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 = 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 = b;code = 98 char = y;code = 121 char = ;code = 32 char = a;code = 97 char = p;code = 112 char = i;code = 105 char = g;code = 103 char = e;code = 101 char = n;code = 110 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = t;code = 116 char = r;code = 114 char = e;code = 101 char = a;code = 97 char = t;code = 116 char = m;code = 109 char = e;code = 101 char = n;code = 110 char = t;code = 116 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = v;code = 118 char = o;code = 111 char = l;code = 108 char = v;code = 118 char = e;code = 101 char = s;code = 115 char = ;code = 32 char = b;code = 98 char = o;code = 111 char = t;code = 116 char = h;code = 104 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = t;code = 116 char = r;code = 114 char = i;code = 105 char = n;code = 110 char = s;code = 115 char = i;code = 105 char = c;code = 99 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = e;code = 101 char = x;code = 120 char = t;code = 116 char = r;code = 114 char = i;code = 105 char = n;code = 110 char = s;code = 115 char = i;code = 105 char = c;code = 99 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 = t;code = 116 char = i;code = 105 char = c;code = 99 char = ;code = 32 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 char = s;code = 115 char = .;code = 46 char = ;code = 32 char = T;code = 84 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = a;code = 97 char = b;code = 98 char = i;code = 105 char = l;code = 108 char = i;code = 105 char = t;code = 116 char = y;code = 121 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = a;code = 97 char = p;code = 112 char = i;code = 105 char = g;code = 103 char = e;code = 101 char = n;code = 110 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = t;code = 116 char = o;code = 111 char = ;code = 32 char = e;code = 101 char = n;code = 110 char = h;code = 104 char = a;code = 97 char = n;code = 110 char = c;code = 99 char = e;code = 101 char = ;code = 32 char = U;code = 85 char = V;code = 86 char = B;code = 66 char = -;code = 45 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 = 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 = m;code = 109 char = a;code = 97 char = y;code = 121 char = ;code = 32 char = e;code = 101 char = x;code = 120 char = p;code = 112 char = l;code = 108 char = a;code = 97 char = i;code = 105 char = n;code = 110 char = ,;code = 44 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = p;code = 112 char = a;code = 97 char = r;code = 114 char = t;code = 116 char = ,;code = 44 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = p;code = 112 char = h;code = 104 char = o;code = 111 char = t;code = 116 char = o;code = 111 char = c;code = 99 char = h;code = 104 char = e;code = 101 char = m;code = 109 char = o;code = 111 char = p;code = 112 char = r;code = 114 char = e;code = 101 char = v;code = 118 char = e;code = 101 char = n;code = 110 char = t;code = 116 char = i;code = 105 char = v;code = 118 char = e;code = 101 char = ;code = 32 char = e;code = 101 char = f;code = 102 char = f;code = 102 char = e;code = 101 char = c;code = 99 char = t;code = 116 char = s;code = 115 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = a;code = 97 char = p;code = 112 char = i;code = 105 char = g;code = 103 char = e;code = 101 char = n;code = 110 char = i;code = 105 char = n;code = 110 char = .;code = 46 char = <;code = 60 char = b;code = 98 char = r;code = 114 char = /;code = 47 char = >;code = 62 result sql = Topical application of the bioflavonoid 4',5,7-trihydroxyflavone (apigenin) to mouse skin effectively reduces the incidence and size of skin tumors caused by UVB exposure. The ability to act as a chemopreventive compound indicates that apigenin treatment alters the molecular events initiated by UVB exposure; however, the effects of apigenin treatment on UVB-irradiated keratinocytes are not fully understood. In the present study, we have used three models of human keratinocytes to study the effect of apigenin treatment on UVB-induced apoptosis: HaCaT human keratinocyte cells, primary keratinocyte cultures isolated from human neonatal foreskin, and human organotypic keratinocyte cultures. Each keratinocyte model was exposed to a moderate dose of UVB (300-1,000 J/m(2)), then treated with apigenin (0-50 micromol/L), and harvested to assess apoptosis by Western blot analysis for poly(ADP)ribose polymerase cleavage, annexin-V staining by flow cytometry, and/or the presence of sunburn cells. Apigenin treatment enhanced UVB-induced apoptosis >2-fold in each of the models tested. When keratinocytes were exposed to UVB, apigenin treatment stimulated changes in Bax localization and increased the release of cytochrome c from the mitochondria compared with UVB exposure alone. Overexpression of the antiapoptotic protein Bcl-2 and expression of a dominant-negative form of Fas-associated death domain led to a reduction in the ability of apigenin to enhance UVB-induced apoptosis. These results suggest that enhancement of UVB-induced apoptosis by apigenin treatment involves both the intrinsic and extrinsic apoptotic pathways. The ability of apigenin to enhance UVB-induced apoptosis may explain, in part, the photochemopreventive effects of apigenin.
Publication: Cancer Res. 2008 Apr 15 ;68(8)::3057-65. :doi: 10.1158/0008-5472.CAN-07-2763.
Publication Date: 2008 Apr 15
Study Author(s): Abu-Yousif, Adnan O;Smith, Kimberly A;Getsios, Spiro;Green, Kathleen J;Van Dross, Rukiyah T;Pelling, Jill C;
Institution: Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas, USA.
Shortcut link to this study:
Topical application of the bioflavonoid 4',5,7-trihydroxyflavone (apigenin) to mouse skin effectively reduces the incidence and size of skin tumors caused by UVB exposure. The ability to act as a chemopreventive compound indicates that apigenin treatment alters the molecular events initiated by UVB exposure; however, the effects of apigenin treatment on UVB-irradiated keratinocytes are not fully understood. In the present study, we have used three models of human keratinocytes to study the effect of apigenin treatment on UVB-induced apoptosis: HaCaT human keratinocyte cells, primary keratinocyte cultures isolated from human neonatal foreskin, and human organotypic keratinocyte cultures. Each keratinocyte model was exposed to a moderate dose of UVB (300-1,000 J/m(2)), then treated with apigenin (0-50 micromol/L), and harvested to assess apoptosis by Western blot analysis for poly(ADP)ribose polymerase cleavage, annexin-V staining by flow cytometry, and/or the presence of sunburn cells. Apigenin treatment enhanced UVB-induced apoptosis >2-fold in each of the models tested. When keratinocytes were exposed to UVB, apigenin treatment stimulated changes in Bax localization and increased the release of cytochrome c from the mitochondria compared with UVB exposure alone. Overexpression of the antiapoptotic protein Bcl-2 and expression of a dominant-negative form of Fas-associated death domain led to a reduction in the ability of apigenin to enhance UVB-induced apoptosis. These results suggest that enhancement of UVB-induced apoptosis by apigenin treatment involves both the intrinsic and extrinsic apoptotic pathways. The ability of apigenin to enhance UVB-induced apoptosis may explain, in part, the photochemopreventive effects of apigenin.
PMID: 18413777