Dietary grape seed proanthocyanidins inhibit UVB-induced cyclooxygenase-2 expression and other inflammatory mediators in UVB-exposed skin and skin tumors of SKH-1 hairless mice.
OBJECTIVE
The purpose of this study was to determine the chemopreventive mechanism of dietary grape seed proanthocyanidins (GSPs) against ultraviolet (UV) radiation-induced skin tumor development in mice.


METHODS
Six-to-seven-week-old SKH-1 hairless mice were subjected to photocarcinogenesis protocol, and exposed to UVB radiation (180 mJ/cm(2)) three times/week for 24 weeks. Mice were fed a standard AIN76A control diet with or without supplementation with grape seed proanthocyanidins (GSPs; 0.2% or 0.5%, w/w). At the termination of the experiment, mice were sacrificed, and skin and skin tumor samples were harvested and subjected to the analysis of biomarkers related to inflammation using immunostaining, western blot analysis, ELISA and real-time PCR.


RESULTS
Dietary GSPs inhibited UVB-induced infiltration of proinflammatory leukocytes and the levels of myeloperoxidase, cyclooxygenase-2 (COX-2), prostaglandin (PG) E(2), cyclin D1 and proliferating cell nuclear antigen (PCNA) in the skin and skin tumors compared to non-GSPs-treated UVB irradiated mouse skin and skin tumors. GSPs also significantly inhibited the levels of proinflammatory cytokines, tumor necrosis factor-alpha (P < 0.01), IL-1beta (P < 0.001) and IL-6 (P < 0.001), in UVB-exposed skin and skin tumors.


CONCLUSIONS
The results from this study clearly suggest that dietary GSPs inhibit photocarcinogenesis in mice through the inhibition of UVB-induced inflammation and mediators of inflammation in mouse skin.
Sharma
Som D
SD
Department of Dermatology, University of Alabama, 1670 University Boulevard, Volker Hall 557, Birmingham, Alabama 35294, USA.
Katiyar
Santosh K
SK
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects; D018890:Chemoprevention; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D004032:Diet; D015232:Dinoprostone / Q000235:genetics / Q000276:immunology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D056604:Grape Seed Extract / Q000494:pharmacology / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000276:immunology*; D051379:Mice; D008812:Mice, Hairless; D044945:Proanthocyanidins / Q000494:pharmacology / Q000627:therapeutic use*; D012867:Skin / Q000187:drug effects / Q000276:immunology / Q000473:pathology / Q000528:radiation effects; D012878:Skin Neoplasms / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D014466:Ultraviolet Rays
D016588:Anticarcinogenic Agents; D000972:Antineoplastic Agents, Phytogenic; D016207:Cytokines; D056604:Grape Seed Extract; C511402:Grape Seed Proanthocyanidins; D018836:Inflammation Mediators; D044945:Proanthocyanidins; D051546:Cyclooxygenase 2; D015232:Dinoprostone