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Anti-Cancer Activity from Natural Plants

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13) Pterostilbene_suppresses_aberrant_crypt_colon_carcinogenesis
Clin Cancer Res. 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 N, Paul S, Hao X, Simi B, Xiao H, Rimando AM, Reddy BS.
Source  Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, USA.

Epidemiologic studies have linked the consumption of fruits and vegetables to reduced risk of several types of cancer. Laboratory animal model studies have provided evidence that stilbenes, phenolic compounds present in grapes and blueberries, play a role in inhibiting the risk of certain cancers. Pterostilbene, a naturally occurring stilbene from blueberries, was tested for its preventive activity against colon carcinogenesis.
EXPERIMENTAL DESIGN:  Experiments were designed to study the inhibitory effect of pterostilbene against the formation of azoxymethane-induced colonic aberrant crypt foci (ACF) preneoplastic lesions in male F344 rats. Beginning at 7 weeks of age, rats were treated with azoxymethane (15 mg/kg body weight s.c., once weekly for 2 weeks). One day after the second azoxymethane treatment, rats were fed experimental diets containing 0 or 40 ppm of pterostilbene. At 8 weeks after the second azoxymethane treatment, all rats were sacrificed, and colons were evaluated for ACF formation and for inhibition of inducible nitric oxide synthase (iNOS) and proliferating cell nuclear antigen. Effects on mucin MUC2 were also determined.
RESULTS:  Administration of pterostilbene for 8 weeks significantly suppressed azoxymethane-induced formation of ACF (57% inhibition, P < 0.001) and multiple clusters of aberrant crypts (29% inhibition, P < 0.01). Importantly, dietary pterostilbene also suppressed azoxymethane-induced colonic cell proliferation and iNOS expression. Inhibition of iNOS expression by pterostilbene was confirmed in cultured human colon cancer cells.
CONCLUSIONS:  The results of the present study suggest that pterostilbene, a compound present in blueberries, is of great interest for the prevention of colon cancer.

14) Pharmacometrics_of_pterostilbene_Phytother_Res_2008
Phytother Res. 2008 Feb;22(2):169-79.  Pharmacometrics of pterostilbene: preclinical pharmacokinetics and metabolism, anticancer, antiinflammatory, antioxidant and analgesic activity.  Remsberg CM, Yáñez JA, Ohgami Y, Vega-Villa KR, Rimando AM, Davies NM.  Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University Pullman, Washington 99164-6534, USA.

The present study evaluated the preclinical pharmacokinetics and pharmacodynamics of trans-pterostilbene, a constituent of some plants. Right jugular vein cannulated male Sprague-Dawley rats were dosed i.v. with 20 mg/kg of pterostilbene and samples were analysed by the reverse phase HPLC method. Serum AUC, serum t(1/2), urine t(1/2), Cl(total) and Vd(beta) were 17.5 +/- 6.6 microg/h/mL, 1.73 +/- 0.78 h, 17.3 +/- 5.6 h, 0.960 +/- 0.025 L/h/kg and 2.41 +/- 1.13 L/kg (mean +/- SEM), respectively. A pterostilbene glucuronidated metabolite was detected in both serum and urine. The in vitro metabolism in rat liver microsomes furthermore suggests phase II metabolism of pterostilbene. Pterostilbene demonstrated concentration-dependent anticancer activity in five cancer cell lines (1-100 microg/mL). An in vitro colitis model showed concentration-dependent suppression of PGE(2) production in the media of HT-29 cells. Antiinflammatory activity was examined by inducing inflammation in canine chondrocytes followed by treatment with pterostilbene (1-100 microg/mL). The results showed decreased levels of MMP-3, sGAG and TNF-alpha compared with control levels. Pterostilbene exhibited concentration-dependent antioxidant capacity measured by the ABTS method. Pterostilbene increased the latency period to response in both tail-flick and hot-plate analgesic tests.

15) Resveratrol_derivatives_cancer_Drug_Discov_Today_2010_Fulda
Drug Discov Today. 2010 Sep;15(17-18):757-65.
Resveratrol and derivatives for the prevention and treatment of cancer. Fulda S.   Institute for Experimental Cancer Research in Pediatrics, Goethe-University, D-60528 Frankfurt, Germany.

There are several  natural derivatives of resveratrol that are structurally similar to resveratrol and are also present in food.  Such resveratrol derivatives might provide promising tools as cancer chemopreventive agents, as well as cancer therapeutics in the prevention and treatment of cancer. This review provides an overview of key derivatives of resveratrol as cancer therapeutics.

Evidence-Based Complementary and Alternative Medicine Volume 2011 (2011), Suppression of Heregulin-β1/HER2-Modulated Invasive and Aggressive Phenotype of Breast Carcinoma by Pterostilbene via Inhibition of Matrix Metalloproteinase-9, p38 Kinase Cascade and Akt Activation

Min-Hsiung Pan,1 Ying-Ting Lin,2 Chih-Li Lin,3 Chi-Shiang Wei,2 Chi-Tang Ho,4 and Wei-Jen Chen21Department of Seafood Science, National Kaohsiung Marine University, Nan-Tzu, Kaohsiung,  Taiwan 2Department of Biomedical Sciences, Chung Shan Medical University, No. 110, Section 1, Chien-Kuo N. Road, Taichung 402,  Taiwan 3Institute of Medicine, Chung Shan Medical University, Taichung 402,  Taiwan 4Department of Food Science, Cook College, Rutgers University, New Brunswick, NJ,  USA

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17) Pterostilbene_apoptosis_ leukemia
Folia Histochem Cytobiol. 2012;50(4):574-80.
Pterostilbene induces cell cycle arrest and apoptosis in MOLT4 human leukemia cells.
Siedlecka-Kroplewska K, Jozwik A, Kaszubowska L, Kowalczyk A, Boguslawski W.
Department of Histology, Medical University of Gdansk, Gdansk, Poland.

Pterostilbene, a polyphenolic compound present in grapes and other fruits, has been demonstrated to inhibit growth and induce apoptosis and autophagy in some cancer cell types. We found that pterostilbene at the IC(90) concentration of 44 -M inhibited proliferation and induced apoptosis in MOLT4 human leukemia cells. Treatment with pterostilbene resulted in a transient accumulation of cells in the G(0)/G(1)-cell cycle phase followed by the S-phase arrest. Pterostilbene-induced apoptotic death of MOLT4 cells was mediated by caspase-3 activation and was accompanied by the disruption of mitochondrial membrane potential, phosphatidylserine externalization and internucleosomal DNA fragmentation. Our results suggest that pterostilbene could serve as a potential additional chemotherapeutic agent for the treatment of leukemia.

commercial product monograph

18) Natural-Pterostilbene  "NATURAL PTEROSTILBENE." by MAJEED, MUHAMMED.

Clin Cancer Res. 2010 Dec 15;16(24):5942-8.
Resveratrol: challenges in translation to the clinic--a critical discussion.Subramanian L, Youssef S, Bhattacharya S, Kenealey J, Polans AS, van Ginkel PR.Department of Ophthalmology and Visual Sciences, Eye Research Institute, and Carbone Cancer Center, University of Wisconsin, Madison, Wisconsin 53792, USA.

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Low cancer survival rates and the serious side effects often associated with current chemotherapeutics highlight the need for new and effective nontoxic anticancer agents. Since 1997 when Jang and colleagues first described resveratrol's ability to inhibit carcinogenesis, it has consistently proven effective at tumor inhibition in diverse human cancer models. This finding has raised the hope that resveratrol would pioneer a novel class of nontoxic chemotherapeutics. As a consequence of initial basic and preclinical studies, resveratrol is now being extensively promoted in the unregulated nutraceutical sector. However, some fundamental aspects of resveratrol's action need to be understood before it can be developed into a clinically viable anticancer drug. These areas pertain to the key mechanism(s) by which resveratrol potentiates its antitumor effects. Current research suggests that these mechanisms might be through novel pathways, requiring an understanding of cellular uptake, sentinel targets, and in vivo biological networks. The metabolism of resveratrol and its bioavailability also warrant further consideration in light of recent in vitro and in vivo studies. Finally, we need to appreciate the sorts of information about resveratrol that may translate between different disease entities. We present a critical discussion of these issues and suggest important experiments that could pave the way to the successful translation of resveratrol to the clinic.

Food Funct. 2012 Nov;3(11):1185-94. 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 ML, Lai CS, Chang YH, Chen WJ, Ho CT, Pan MH.Department of Seafood Science, National Kaohsiung Marine University, Nan-Tzu, Kaohsiung 811, Taiwan. Email address removed

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.

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Jeffrey Dach MD is a physician and author of two books, Natural Medicine 101, and Bioidentical Hormones 101, both available on Amazon, or as a free e-book on his web sites. Dr. Dach is founder and chief medical officer of TrueMedMD, a clinic in (more...)

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