Prevention of Cancer
Clin CancerRes.2007 Jan 1;13(1):350-5.
Pterostilbene, an active constituent of blueberries, suppresses aberrant crypt foci formation in the azoxymethane-induced colon carcinogenesis model in rats.
Suh N1,Paul S, Hao X, Simi B, Xiao H, Rimando AM, Reddy BS.
Abstract
PURPOSE: Epidemiologic studies have linked the consumption of fruits and vegetables to
EXPERIMENTAL DESIGN: Experiments were designed to study the inhibitory effect of
RESULTS: Administration of
CONCLUSIONS: The results of the present study suggest that pterostilbene, a compound present in blueberries, is of great interest
PMID: 17200374
Carcinogenesis.2010 Jul;31(7):1272-8. doi: 10.1093/carcin/bgq004. Epub 2010 Jan 8.
Dietary intake of pterostilbene, a constituent of blueberries, inhibits the beta-catenin/p65 downstream signaling pathway and colon carcinogenesis in rats.
Paul S1, DeCastro AJ, Lee HJ, Smolarek AK, So JY, Simi B, Wang CX, Zhou R, Rimando AM, Suh N.
Abstract
Stilbenes are phytochemicals present in grapes, berries, peanuts
PMID: 20061362
J Agric Food Chem.2010 Aug 11;58(15):8833-41. doi: 10.1021/jf101571z.
Pterostilbene inhibits colorectal aberrant crypt foci (ACF) and colon carcinogenesis via suppression of multiple signal transduction pathways in azoxymethane-treated mice.
Chiou YS1, Tsai ML, Wang YJ, Cheng AC, Lai WM, Badmaev V, Ho CT, Pan MH.
Abstract
Pterostilbene (PS), a natural dimethylated
PMID: 20681671
J Agric Food Chem.2011 Mar 23;59(6):2725-33. doi: 10.1021/jf2000103. Epub 2011 Feb 28.
Pterostilbene is more potent than resveratrol in preventing azoxymethane (AOM)-induced colon tumorigenesis via activation of the NF-E2-related factor 2 (Nrf2)-mediated antioxidant signaling pathway.
Chiou YS1, Tsai ML, Nagabhushanam K, Wang YJ, Wu CH, Ho CT, Pan MH.
Abstract
Inflammatory bowel diseases have been a risk factor of colorectal cancer (CRC). The reactive oxygen species (ROS) generated by inflammatory cells create oxidative stress and contribute to neoplastic transformation, proliferation, and even metastasis. Previously, resveratrol (RS) and pterostilbene (PS) had been reported to prevent chemical-induced colon carcinogenesis by anti-inflammatory and pro-apoptotic properties. In this study, we investigated whether RS and PS could prevent the azoxymethane (AOM)-induced colon tumorigenesis via antioxidant action and to explore possible molecular mechanisms. Male BALB/c mice were injected with AOM (5 mg/kg of body weight) with or without RS or PS, and at the end of the protocol, all of the mice were euthanized and colons were analyzed. Administrations of PS can be more effective than RS in reducing AOM-induced formation of aberrant crypt foci (ACF), lymphoid nodules (LNs), and tumors. We also find that PS is functioning more effectively than RS to reduce nuclear factor-κB (NF-κB) activation by inhibiting the phosphorylation of protein kinase C-β2 (PKC-β2) and decreasing downstream target gene expression, including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and aldose reductase (AR) in mouse colon stimulated by AOM. Moreover, administration of RS and PS for 6 weeks significantly enhanced expression of antioxidant enzymes, such as heme oxygenase-1 (HO-1) and glutathione reductase (GR), via activation of NF-E2-related factor 2 (Nrf2) signaling. When the above findings are taken together, they suggest that both stilbenes block cellular inflammation and oxidative stress through induction of HO-1 and GR, thereby preventing AOM-induced colon carcinogenesis. In comparison, PS was a more potent chemopreventive agent than RS for the prevention of colon cancer. This is also the first study to demonstrate that PS is
PMID: 21355597
Asian Pac J CancerPrev.2012;13(12):6403-7.
Potential chemoprevention activity of pterostilbene by enhancing the detoxifying enzymes in the HT-29 cell line.
Abstract
Detoxifying enzymes are present in most epithelial cells of the human gastrointestinal tract where they protect against xenobiotics which may cause cancer. Induction of examples such as glutathione S-transferase (GST) and its thiol conjugate, glutathione (GSH) as well as NAD(P)H:
PMID: 23464466
J Agric Food Chem.2012 Jun 13;60(23):5693-708. doi: 10.1021/jf204084f. Epub 2012 Feb 22.
Influence of berry polyphenols on receptor signaling and cell-death pathways: implications for breast cancer prevention.
Aiyer HS1, Warri AM, Woode DR, Hilakivi-Clarke L, Clarke R.
Abstract
Breast cancer is the most commonly diagnosed cancer among women worldwide. Many women have become more aware of the benefits of increasing fruit consumption, as part of a healthy lifestyle, for the prevention of cancer. The mechanisms by which fruits, including berries, prevent breast cancer can be partially explained by exploring their interactions with pathways known to influence cell proliferation and evasion of cell-death. Two receptor pathways, estrogen receptor (ER) and tyrosine kinase receptors, especially the epidermal growth factor receptor (EGFR) family, are drivers of cell proliferation and play a significant role in the development of both primary and recurrent breast cancer. There is strong evidence to show that several phytochemicals present in berries such as cyanidin, delphinidin, quercetin, kaempferol, ellagic acid, resveratrol, and pterostilbene interact with and alter the effects of these pathways. Furthermore, they also induce cell death (apoptosis and autophagy) via their influence on kinase signaling. This review summarizes in vitro data regarding the interaction of berry polyphenols with the specific receptors and the mechanisms by which they induce cell death. This paper also presents in vivo data of primary breast cancer prevention by individual compounds and whole berries. Finally, a possible role for berries and berry compounds in the prevention of breast cancer and a perspective on the areas that require further research are presented.
PMID: 22300613
Food Funct.2012 Nov;3(11):1185-94. doi: 10.1039/c2fo30105a.
Pterostilbene, a natural analogue of resveratrol, potently inhibits 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse skin carcinogenesis.
Tsai ML1, Lai CS, Chang YH, Chen WJ, Ho CT, Pan MH.
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.
PMID: 22842666
J Agric Food Chem.2012 Nov 21;60(46):11533-41. doi: 10.1021/jf302778a. Epub 2012 Nov 7.
Chemopreventive effects of pterostilbene on urethane-induced lung carcinogenesis in mice via the inhibition of EGFR-mediated pathways and the induction of apoptosis and autophagy.
Chen RJ1, Tsai SJ, Ho CT, Pan MH, Ho YS, Wu CH, Wang YJ.
Abstract
Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer deaths globally. Due to the lack of successful chemopreventive agents for lung cancer, there is an emerging need to evaluate new and effective agents for lung cancer prevention. Pterostilbene, a naturally occurring analogue of resveratrol, has been reported to be an effective chemopreventive agent against many cancers. The aim of this study is to investigate the chemopreventive effects of pterostilbene in urethane-induced murine lung tumors. Pretreatment with pterostilbene at 50 or 250 mg/kg significantly reduced tumor multiplicity by 26 and 49%, respectively. Pterostilbene also significantly inhibited tumor volume by 25 and 34% and decreased the tumor burden per mouse by 45 and 63%, respectively. The mechanisms by which pterostilbene suppresses lung tumorigenesis have been investigated in lung tissues and homogenates. The results indicate that the pterostilbene-mediated chemopreventive effects in vivo were a result of the inhibition of epidermal growth factor receptor (EGFR) and its downstream pathways, leading to retarded cell cycle progression, and of the induction of apoptosis and autophagy during urethane-induced lung tumorigenesis.
PMID: 23113763
Free Radic Biol Med.2015 Aug;85:1-11. doi: 10.1016/j.freeradbiomed.2015.03.027. Epub 2015 Apr 4.
Topical treatment with pterostilbene, a natural phytoalexin, effectively protects hairless mice against UVB radiation-induced skin damage and carcinogenesis.
Sirerol JA1,Feddi F2, Mena S1, Rodriguez ML1, Sirera P1, Aupí M1, Pérez S1, Asensi M3, Ortega A3, Estrela JM4.
Abstract
The aim of our study was to investigate in the SKH-1 hairless mouse model the effect of pterostilbene(Pter), a natural dimethoxy analog of resveratrol (Resv), against procarcinogenic ultraviolet B radiation (UVB)-induced skin damage. Pter prevented acute UVB (360 mJ/cm(2))-induced increase in skin fold, thickness, and redness, as well as photoaging-associated skin wrinkling and hyperplasia. Pter, but not Resv, effectively prevented chronic UVB (180 mJ/cm(2), three doses/week for 6 months)-induced skin carcinogenesis (90% of Pter-treated mice did not develop skin carcinomas, whereas a large number of tumors were observed in all controls). This anticarcinogenic effect was associated with (a) maintenance of skin antioxidant defenses (i.e., glutathione (GSH) levels, catalase, superoxide, and GSH peroxidase activities) close to control values (untreated mice) and (b) an inhibition of UVB-induced oxidative damage (using as biomarkers 8-hydroxy-2′-deoxyguanosine, protein carbonyls, and isoprostanes). The molecular mechanism underlying the photoprotective effect elicited by Pter was further evaluated using HaCaT immortalized human keratinocytes and was shown to involve potential modulation of the Nrf2-dependent antioxidant response.
Copyright © 2015 Elsevier Inc. All rights reserved.
KEYWORDS: Free radicals; Oxidative stress; Photocarcinogenesis; Phytochemicals; Polyphenols; Pterostilbene; Resveratrol; Skin damage; Stilbenes; UV radiation
PMID: 25845487
Food Chem Toxicol.2017 Jan;99:182-189. doi: 10.1016/j.fct.2016.11.007. Epub 2016 Nov 9.
Enhanced chemoprevention by the combined treatment of pterostilbeneand lupeol in B[a]P-induced mouse skin tumorigenesis.
Abstract
The present study is aimed to evaluate the inhibitory effect of the combination of two phytochemicals; pterostilbeneand lupeol (generally obtained from blue berries, grapes, white cabbage, green pepper, olive and mangoes) on mouse skin tumorigenesis. We hypothesized that the concomitant topical treatment of selected phytochemicals would lead to improved impediment of skin cancer. Swiss albino mice (n = 25) received a topical dose of Benzo[a]pyrene (B[a]P, 5 μg/animal) with pre/post application of pterostilbene(16 μM/0.2 ml acetone/animal) and/or lupeol (500 μM/0.2 ml acetone/animal) for 32 weeks. Results showed that pterostilbeneand/or lupeol treatment resulted in a significant delay in onset of tumorigenesis. However, a more promising effect on tumor suppression was noted with the combination of both the phytochemicals. A significant reduction in average tumor volume, cumulative number of tumors and tumor multiplicity was recorded in combination treated group. The histopathological analysis illustrated the marked suppression in epidermal hyperplasia and necrotic cells in combination treated groups. Our study suggests that the combination of pterostilbeneand lupeol was more effective in prevention of skin canceras compared to either of the phytochemical alone. Therefore, the combined treatment of phytochemicals has better potential to prevent skin carcinogenesis.
Copyright © 2016 Elsevier Ltd. All rights reserved.
KEYWORDS: Benzo[a]pyrene; Chemoprevention; Lupeol; Phytochemical; Pterostilbene
PMID: 27836749