title: Delphinidin, an anthocyanidin in pigmented fruits and vegetables, protects human HaCaT keratinocytes and mouse skin against UVB-mediated oxidative stress and apoptosis.
abstract: 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 microM for 24 hours) protected against UVB (15-30 mJ/cm2, 24 hours)-mediated (i) decrease in cell viability and (ii) 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.
authors.affiliation: Department of Dermatology, University of Wisconsin, Madison, Wisconsin 53706, USA.
authors.forename: Farrukh
authors.initials: F
authors.lastname: Afaq
authors.forename: Deeba N
authors.initials: DN
authors.lastname: Syed
authors.forename: Arshi
authors.initials: A
authors.lastname: Malik
authors.forename: Naghma
authors.initials: N
authors.lastname: Hadi
authors.forename: Sami
authors.initials: S
authors.lastname: Sarfaraz
authors.forename: Mee-Hyang
authors.initials: MH
authors.lastname: Kweon
authors.forename: Naghma
authors.initials: N
authors.lastname: Khan
authors.forename: Mohammad Abu
authors.initials: MA
authors.lastname: Zaid
authors.forename: Hasan
authors.initials: H
authors.lastname: Mukhtar
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000872:Anthocyanins / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D020287:In Situ Nick-End Labeling; D015603:Keratinocytes / Q000528:radiation effects*; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D008812:Mice, Hairless; D018384:Oxidative Stress / Q000187:drug effects* / Q000528:radiation effects; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D011740:Pyrimidine Dimers / Q000378:metabolism; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects / Q000528:radiation effects*; D051028:bcl-2-Associated X Protein / Q000032:analysis
chemical_list: D000872:Anthocyanins; D000975:Antioxidants; D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D011740:Pyrimidine Dimers; D011837:Radiation-Protective Agents; D051028:bcl-2-Associated X Protein; D000080242:8-Hydroxy-2'-Deoxyguanosine; D020169:Caspases; C017185:delphinidin; D003849:Deoxyguanosine