Delphinidin, an anthocyanidin in pigmented fruits and vegetables, protects human HaCaT keratinocytes and mouse skin against UVB-mediated oxidative stress and apoptosis

被引:183
作者
Afaq, Farrukh [1 ]
Syed, Deeba N. [1 ]
Malik, Arshi [1 ]
Hadi, Naghma [1 ]
Sarfaraz, Sami [1 ]
Kweon, Mee-Hyang [1 ]
Khan, Naghma [1 ]
Abu Zaid, Mohammad [1 ]
Mukhtar, Hasan [1 ]
机构
[1] Univ Wisconsin, Med Sci Ctr, Dept Dermatol, Madison, WI 53706 USA
关键词
D O I
10.1038/sj.jid.5700510
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
Solar UV radiation, in particular its UVB component, is the primary cause of many adverse biological effects, the most damaging of which is skin cancer. Here, we assessed the photochemopreventive effect of delphinidin, a major anthocyanidin present in many pigmented fruits and vegetables, on UVB-mediated responses in human immortalized HaCaT keratinocytes and SKH-1 hairless mouse skin. We found that pretreatment of cells with delphinidin (1-20 mu M for 24 hours) protected against UVB (15-30 mJ/cm(2), 24 hours)-mediated (i) decrease in cell viability and 00 induction of apoptosis. Furthermore, we found that pretreatment of HaCaT cells with delphinidin inhibited UVB-mediated (i) increase in lipid peroxidation; (ii) formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG); (iii) decrease in proliferating cell nuclear antigen expression; (iv) increase in poly(ADP-ribose) polymerase cleavage; (v) activation of caspases; (vi) increase in Bax; (vii) decrease in Bcl-2; (viii) upregulation of Bid and Bak; and (ix) downregulation of Bcl-xL. Topical application of delphinidin (1 mg/0.1 ml DMSO/mouse) to SKH-1 hairless mouse skin inhibited UVB-mediated apoptosis and markers of DNA damage such as cyclobutane pyrimidine dimers and 8-OHdG. Taken together our results suggest that treatment of HaCaT cells and mouse skin with delphinidin inhibited UVB-mediated oxidative stress and reduced DNA damage, thereby protecting the cells from UVB-induced apoptosis.
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页码:222 / 232
页数:11
相关论文
共 40 条
[1]   Photochemoprevention of ultraviolet B signaling and photocarcinogenesis [J].
Afaq, F ;
Adhami, VM ;
Mukhtar, H .
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS, 2005, 571 (1-2) :153-173
[2]  
Afaq F, 2006, J INVEST DERMATOL, V126, P141
[3]   Effects of solar radiation on cutaneous detoxification pathways [J].
Afaq, F ;
Mukhtar, H .
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY, 2001, 63 (1-3) :61-69
[4]   Repair of U/G and U/A in DNA by UNG2-associated repair complexes takes place predominantly by short-patch repair both in proliferating and growth-arrested cells [J].
Akbari, M ;
Otterlei, M ;
Peña-Diaz, J ;
Aas, PA ;
Kavli, B ;
Liabakk, NB ;
Hagen, L ;
Imai, K ;
Durandy, A ;
Slupphaug, G ;
Krokan, HE .
NUCLEIC ACIDS RESEARCH, 2004, 32 (18) :5486-5498
[5]   TP53 TUMOR-SUPPRESSOR GENE AND SKIN CARCINOGENESIS [J].
BASSETSEGUIN, N ;
MOLES, JP ;
MILS, V ;
DEREURE, O ;
GUILHOU, JJ .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1994, 103 (05) :S102-S106
[6]   Prevention of non-melanoma skin cancer by targeting ultraviolet-B-light signalling [J].
Bowden, GT .
NATURE REVIEWS CANCER, 2004, 4 (01) :23-35
[7]   Modulation of endoplasmic reticulum-bound cholesterol regulatory enzymes by iron/ascorbate-mediated lipid peroxidation [J].
Brunet, S ;
Thibault, L ;
Lepage, G ;
Seidman, EG ;
Dubé, N ;
Levy, E .
FREE RADICAL BIOLOGY AND MEDICINE, 2000, 28 (01) :46-54
[8]   Protective effect of topically applied olive oil against photocarcinogenesis following UVB exposure of mice [J].
Budiyanto, A ;
Ahmed, NU ;
Wu, A ;
Bito, T ;
Nikaido, O ;
Osawa, T ;
Ueda, M ;
Ichihashi, M .
CARCINOGENESIS, 2000, 21 (11) :2085-2090
[9]   Ultraviolet radiation-mediated damage to cellular DNA [J].
Cadet, J ;
Sage, E ;
Douki, T .
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS, 2005, 571 (1-2) :3-17
[10]   Proteases for cell suicide: Functions and regulation of caspases [J].
Chang, HY ;
Yang, XL .
MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS, 2000, 64 (04) :821-+