8) http://www.ncbi.nlm.nih.gov/
http://www.ncbi.nlm.nih.gov/
Am J Transl Res. 2012;4(1):44-51. Epub 2012 Jan 5.
Pterostilbene simultaneously induces apoptosis, cell cycle arrest and
cyto-protective autophagy in breast cancer cells.Wang Y, Ding L, Wang X,
Zhang J, Han W, Feng L, Sun J, Jin H, Wang XJ.
As a nature phytoalexin found in grapes, resveratrol has been proposed as a potential drug for cancer chemoprevention and treatment. However, its poor bioavailability limits its potential clinical application. Pterostilbene, the natural dimethylated analog of resveratrol with greater bioavailability, was confirmed to inhibit tumor growth both in vivo and in vitro, demonstrating its potential for further clinical application. In the current study, we found that pterostilbene could markedly inhibit the growth of two independent breast cancer cell lines. Both apoptosis and cell cycle arrest as well as the inhibition of wnt singling was induced by pterostilbene. The dominant-active mutant of ß-catenin could reverse the growth inhibitory effect of pterostilbene, indicating that the inhibition of wnt signaling is important to the growth inhibitory effect of pterostilbene. Interestingly, pterostilbene induced autophagy and blockage of autophagy augmented pterostilbene-induced growth inhibition, suggesting that the combination of autophagy inhibitors with pterostilbene and other therapeutics such as endocrine drugs could serve as a new and promising strategy for the treatment of breast cancer cells.
2012
9) http://www.ncbi.nlm.nih.gov/
http://www.ncbi.nlm.nih.gov/
PLoS One. 2012;7(9):
Pterostilbene-induced tumor cytotoxicity: a lysosomal membrane
permeabilization-dependent mechanism. Mena S, Rodrà guez ML, Ponsoda X,
Estrela JM, Jà �à �ttela M, Ortega AL. Source Green Molecular, Valencia,
Spain.
The phenolic phytoalexin resveratrol is well known for its health-promoting and anticancer properties. Its potential benefits are, however, limited due to its low bioavailability. Pterostilbene, a natural dimethoxylated analog of resveratrol, presents higher anticancer activity than resveratrol. The mechanisms by which this polyphenol acts against cancer cells are, however, unclear. Here, we show that pterostilbene effectively inhibits cancer cell growth and stimulates apoptosis and autophagosome accumulation in cancer cells of various origins. However, these mechanisms are not determinant in cell demise.
Pterostilbene promotes cancer cell death via a mechanism involving lysosomal membrane permeabilization. Different grades of susceptibility were observed among the different cancer cells depending on their lysosomal heat shock protein 70 (HSP70) content, a known stabilizer of lysosomal membranes. A375 melanoma and A549 lung cancer cells with low levels of HSP70 showed high susceptibility to pterostilbene, whereas HT29 colon and MCF7 breast cancer cells with higher levels of HSP70 were more resistant. Inhibition of HSP70 expression increased susceptibility of HT29 colon and MCF7 breast cancer cells to pterostilbene. Our data indicate that lysosomal membrane permeabilization is the main cell death pathway triggered by pterostilbene.
2013
10) http://www.ncbi.nlm.nih.gov/
http://www.ncbi.nlm.nih.gov/
PLoS One. 2013 May 3;8(5) Pterostilbene Exerts Antitumor Activity via
the Notch1 Signaling Pathway in Human Lung Adenocarcinoma Cells. Yang
Y, Yan X, Duan W, Yan J, Yi W, Liang Z, Wang N, Li Y, Chen W, Yu S, Jin
Z, Yi D. Department of Cardiovascular Surgery, Xijing Hospital, The
Fourth Military Medical University, Xi'an City, China.
In this study, we investigated the antitumor activity of PTE against human lung adenocarcinoma in vitro and in vivo and explored the role of the Notch1 signaling pathway in this process. PTE treatment resulted in a dose- and time-dependent decrease in the viability of A549 cells. Additionally, PTE exhibited strong antitumor activity, as evidenced not only by a reduced mitochondrial membrane potential (MMP) and a decreased intracellular glutathione content but also by increases in the apoptotic index and the level of reactive oxygen species (ROS). Furthermore, PTE treatment induced the activation of the Notch1 Intracellular Domain (NICD) protein and activated Hes1. DAPT (a gamma secretase inhibitor) and Notch1 siRNA prevented the induction of NICD and Hes1 activation by PTE treatment and sensitized the cells to PTE treatment. The down-regulation of Notch signaling also prevented the activation of pro-survival pathways (most notably the PI3K/Akt pathway) after PTE treatment. In summary, lung adenocarcinoma cells may enhance Notch1 activation as a protective mechanism in response to PTE treatment.
2010
11) http://www.ncbi.nlm.nih.gov/
J Surg Res. 2010 Jun 15;161(2):195-201.
Pterostilbene inhibits breast cancer in vitro through mitochondrial depolarization and induction of caspase-dependent apoptosis. Alosi JA, McDonald DE, Schneider JS, Privette AR, McFadden DW. University of Vermont, Burlington, Vermont, USA.
Epidemiologic studies suggest that diets
high in fruits and vegetables reduce cancer risk. Resveratrol, a
compound present in grapes, has been shown to inhibit a variety of
primary tumors. Pterostilbene, an analogue of resveratrol found in blueberries,
has both antioxidant and antiproliferative properties. We hypothesized
that pterostilbene would induce apoptosis and inhibit breast cancer cell
growth in vitro.
METHODS: Breast cancer cells were treated with graduated doses of pterostilbene.
Cell viability was measured by MTT assay. Apoptosis was evaluated via
DNA fragmentation assay and TUNEL assay. Apo-ONE caspase-3/7 assay was
used to evaluate caspase activity. Flow cytometry was used to evaluate
mitochondrial depolarization, superoxide formation, and cell cycle.
Student's t-test and two-way ANOVA with Bonferroni posttests were
utilized for statistical analysis.
RESULTS: Pterostilbene decreased
breast cancer cell viability in a concentration- and time-dependent
manner. Pterostilbene treatment increased caspase-3/7 activity and
apoptosis in both cell lines. Caspase-3/7 inhibitors completely reversed
pterostilbene's effects on cell viability. Pterostilbene treatment
triggered mitochondrial depolarization, increased superoxide anion, and
caused alteration in cell cycle.
CONCLUSIONS: Pterostilbene
treatment inhibits the growth of breast cancer in vitro through
caspase-dependent apoptosis. Mitochondrial membrane
depolarization
and increased superoxide anion may contribute to the activation
downstream effector caspases. Caspase inhibition leads to complete
reversal of pterostilbene's effect on cell viability. Further in vitro
mechanistic studies and in vivo experiments are warranted to determine
its potential for the treatment of breast cancer.
2006
12) Pharmacometrics_of_Pterostilbenes_Curr_Clin_Pharmacol_2006_Davies
Curr Clin Pharmacol. 2006 Jan;1(1):81-101.
Pharmacometrics of stilbenes: seguing towards the clinic.
Roupe KA, Remsberg CM, Yà �à �ez JA, Davies NM.
Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Pullman, Washington 99164-6534, USA.
Stilbenes are small molecular weight (approximately 200-300 g/mol), naturally occurring compounds and are found in a wide range of plant sources, aromatherapy products, and dietary supplements. These molecules are synthesized via the phenylpropanoid pathway and share some structural similarities to estrogen. Upon environmental threat, the plant host activates the phenylpropanoid pathway and stilbene structures are produced and subsequently secreted. Stilbenes act as natural protective agents to defend the plant against viral and microbial attack, excessive ultraviolet exposure, and disease. One stilbene, resveratrol, has been extensively studied and has been shown to possess potent anti-cancer, antiinflammatory and anti-oxidant activities. Found primarily in the skins of grapes, resveratrol is synthesized by Vitis vinifera grapevines in response to fungal infection or other environmental stressors. Considerable research showing resveratrol to be an attractive candidate in combating a wide variety of cancers and diseases has fueled interest in determining the disease-fighting capabilities of other structurally similar stilbene compounds. The purpose of this review is to describe four such structurally similar stilbene compounds, piceatannol, pinosylvin, rhapontigenin, and pterostilbene and detail some current pharmaceutical research and highlight their potential clinical applications.
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