3'-Hydroxypterostilbene Inhibits 7,12-Dimethylbenz[a]anthracene (DMBA)/12-O-Tetradecanoylphorbol-13-Acetate (TPA)-Induced Mouse Skin Carcinogenesis.
BACKGROUND
A natural pterostilbene analogue isolated from the herb Sphaerophysa salsula, 3'-hydroxypterostilbene (HPSB), exhibits antiproliferative activity in several cancer cell lines; however, the inhibitory effects of HPSB on skin carcinogenesis remains unclear.


PURPOSE
The aim of this study was to evaluate the inhibitory effects of HPSB on two-stage skin carcinogenesis in mice and its potential mechanism.


STUDY DESIGN AND METHODS
This study investigated the anti-inflammatory and anti-tumor effects of HPSB in the 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated acute skin inflammation and 7,12-dimethylbenz[a]anthracene (DMBA)/TPA-induced two-stage skin carcinogenesis model. In addition, the effects of HPSB on the modulation of the phase I and phase II metabolizing enzymes in the DMBA-induced HaCaT cell model were investigated.


RESULTS
The results provide evidence that topical treatment with HPSB significantly inhibits TPA-induced epidermal hyperplasia and leukocyte infiltration through the down-regulation of cyclooxygenase-2 (COX-2), matrix metalloprotein-9 (MMP-9), and ornithine decarboxylase (ODC) protein expression in mouse skin. Furthermore, HPSB suppresses DMBA/TPA-induced skin tumor incidence and multiplicity via the inhibition of proliferating cell nuclear antigen (PCNA), Cyclin B1 and cyclin-dependent kinase 1 (CDK1) expression in the two-stage skin carcinogenesis model. In addition, pretreatment with HPSB markedly reduces DMBA-induced cytochrome P450 1A1 (CYP1A1) and cytochrome P450 1B1 (CYP1B1) gene expression in human keratinocytes; however, HPSB does not significantly affect the gene expression of the phase II enzymes.


CONCLUSION
This is the first study to show that topical treatment with HPSB prevents mouse skin tumorigenesis. Overall, our study suggests that natural HPSB may serve as a novel chemopreventive agent capable of preventing carcinogen activation and inflammation-associated tumorigenesis.
['Lee|Pei-Sheng|PS|', 'Chiou|Yi-Shiou|YS|', 'Chou|Pin-Yu|PY|', 'Nagabhushanam|Kalyanam|K|', 'Ho|Chi-Tang|CT|', 'Pan|Min-Hsiung|MH|']
D015127:9,10-Dimethyl-1,2-benzanthracene D000287:Administration, Topical D000818:Animals D000894:Anti-Inflammatory Agents, Non-Steroidal D016588:Anticarcinogenic Agents D002273:Carcinogens D051546:Cyclooxygenase 2 D003875:Drug Eruptions D005260:Female D005786:Gene Expression Regulation D006801:Humans D015603:Keratinocytes D008813:Mice, Inbred ICR D009955:Ornithine Decarboxylase D012878:Skin Neoplasms D013267:Stilbenes D013755:Tetradecanoylphorbol Acetate
7,12-Dimethylbenz[a]anthracene 12-O-Tetradecanoylphorbol-13-acetate Chemoprevention 3′-hydroxypterostilbene Anti-inflammation