4.7 Article

3′-Hydroxypterostilbene Inhibits 7,12-Dimethylbenz [a]anthracene (DMBA)/12-0-Tetradecanoylphorbol-13-Acetate (TPA)-Induced Mouse Skin Carcinogenesis

Journal

PHYTOMEDICINE
Volume 81, Issue -, Pages -

Publisher

ELSEVIER GMBH
DOI: 10.1016/j/phymed.2020.153432

Keywords

Anti-inflammation; Chemoprevention; 3 '-hydroxypterostilbene; 7,12-Dimethylbenz[a]anthracene; 12-O-Tetradecanoylphorbol-13-acetate

Funding

  1. Ministry of Science and Technology, Taiwan [108-2320-B-002 -016 -MY3, 109-2320-B-002 -012 -MY3]

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The study demonstrated that HPSB inhibits TPA-induced skin inflammation and DMBA/TPA-induced skin carcinogenesis in mice by down-regulating key proteins involved in the processes. Additionally, HPSB also suppresses the expression of certain genes involved in carcinogen activation, suggesting its potential as a chemopreventive agent.
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-dimethylbenzlalanthracene (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.

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