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.

Pterostilbene induces cell cycle arrest and apoptosis in MOLT4 human leukemia cells

“…Recently, many in vitro and in vivo studies have indicated that pterostilbene may be a promising chemotherapeutic agent [7][8][9][10][11][12][13][14][15][16][17][18]. In the present study, we have presented novel observations that pterostilbene, a natural resveratrol analogue, induced cell cycle arrest and apoptosis in MOLT4 human leukemia cells.…”

“…It has been found that dietary administration of pterostilbene effectively reduced azoxymethane--induced formation of colonic aberrant crypt foci, pre- www.fhc.viamedica.pl neoplastic lesions and adenomas in mice [16]. Moreover, pterostilbene exerted chemopreventive effects in urethane-induced murine lung tumours [17] and inhibited 7,12-dimethylbenz[a]anthracene (DMBA)/ /TPA-induced skin tumour formation [18].…”

Pterostilbene protects against acute renal ischemia reperfusion injury and inhibits oxidative stress, inducible nitric oxide synthase expression and inflammation in rats via the Toll‑like receptor 4/nuclear factor‑κB signaling pathway

“…In the present study, Pter treatment significantly suppressed the expression levels of IL-1β, IL-6 and TNF-α, and significantly increased IL-10 expression levels in renal IRI rats. Notably, Tsai et al (22) revealed that Pter inhibited mouse skin carcinogenesis via inhibition of iNOS production and downregulated the inflammatory response.…”

Differences in the Glucuronidation of Resveratrol and Pterostilbene: Altered Enzyme Specificity and Potential Gender Differences

“…It is a naturally occurring dimethylated analog of resveratrol, but is predicted to have a longer half-life due to the 3 position being methylated and, therefore, being unable to be glucuronidated at this position. 19) Pterostilbene has been shown to be equally or significantly more potent than resveratrol in several biological assays in mice including inhibition of skin, 20) colon, 21) and liver 22) cancer. Although pterostilbene-4′-O-glucuronide has been characterized as a major metabolite for pterostilbene, 23) the UGTs responsible for its glucuronidation have not been examined previously, nor have gender differences been assessed.…”