title: Pterostilbene, a natural analogue of resveratrol, potently inhibits 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse skin carcinogenesis.
abstract: We reported previously that pterostilbene, a natural analogue of resveratrol from blueberries, strongly suppressed lipopolysaccharide-induced up-expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in murine macrophages. In this study, we further investigated pterostilbene's molecular mechanism of action and its anti-tumor properties. Pretreatment with pterostilbene has resulted in the reduction of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced nuclear translocation of the nuclear factor-κB (NFκB) subunits. Pterostilbene also reduced TPA-induced phosphorylation of IκBα and p65 and caused subsequent degradation of IκBα. Moreover, pterostilbene markedly suppressed TPA-induced activation of extracellular signal-regulated kinase (ERK)1/2, p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK)1/2, phosphatidylinositol 3-kinase (PI3K) and Akt, which are upstream of NFκB and activator protein 1 (AP-1). Furthermore, pterostilbene significantly inhibited 7,12-dimethylbenz[a]anthracene (DMBA)/TPA-induced skin tumor formation measured by the tumor multiplicity of papillomas at 20 weeks. The presented data has, for the first time, revealed that pterostilbene is an effective anti-tumor agent that functions by downregulating inflammatory iNOS and COX-2 gene expression in mouse skin. It is suggested that pterostilbene is a novel functional agent capable of preventing inflammation-associated tumorigenesis.
authors: Department of Seafood Science, National Kaohsiung Marine University, Nan-Tzu, Kaohsiung 811, Taiwan. mltasi@mail.nkmu.eud.tw
authors: Mei-Ling
authors: ML
authors: Tsai
authors: Ching-Shu
authors: CS
authors: Lai
authors: Yen-Hui
authors: YH
authors: Chang
authors: Wei-Jen
authors: WJ
authors: Chen
authors: Chi-Tang
authors: CT
authors: Ho
authors: Min-Hsiung
authors: MH
authors: Pan
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D007249:Inflammation; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D000077185:Resveratrol; D012867:Skin / Q000201:enzymology / Q000473:pathology; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D013267:Stilbenes / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D013267:Stilbenes; C107773:pterostilbene; D015127:9,10-Dimethyl-1,2-benzanthracene; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D013755:Tetradecanoylphorbol Acetate; D000077185:Resveratrol