Pterostilbene simultaneously induces apoptosis, cell cycle arrest and cyto-protective autophagy in breast cancer cells.

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 β-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.

[1]  M. Tsai,et al.  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. , 2011, Journal of agricultural and food chemistry.

[2]  S. Shankar,et al.  Resveratrol Inhibits Pancreatic Cancer Stem Cell Characteristics in Human and KrasG12D Transgenic Mice by Inhibiting Pluripotency Maintaining Factors and Epithelial-Mesenchymal Transition , 2011, PloS one.

[3]  Raj Kumar,et al.  Resveratrol in cancer management: where are we and where we go from here? , 2011, Annals of the New York Academy of Sciences.

[4]  I. Kapetanovic,et al.  Pharmacokinetics, oral bioavailability, and metabolic profile of resveratrol and its dimethylether analog, pterostilbene, in rats , 2011, Cancer Chemotherapy and Pharmacology.

[5]  Ying-Jan Wang,et al.  Pterostilbene induces autophagy and apoptosis in sensitive and chemoresistant human bladder cancer cells. , 2010, Molecular nutrition & food research.

[6]  D. Mcfadden,et al.  Pterostilbene and tamoxifen show an additive effect against breast cancer in vitro. , 2010, American journal of surgery.

[7]  M. Tsai,et al.  Pterostilbene inhibits colorectal aberrant crypt foci (ACF) and colon carcinogenesis via suppression of multiple signal transduction pathways in azoxymethane-treated mice. , 2010, Journal of agricultural and food chemistry.

[8]  Po-Len Liu,et al.  Resveratrol inhibits human lung adenocarcinoma cell metastasis by suppressing heme oxygenase 1-mediated nuclear factor-kappaB pathway and subsequently downregulating expression of matrix metalloproteinases. , 2010, Molecular nutrition & food research.

[9]  J. Sung,et al.  Activation of 5-lipoxygenase is required for nicotine mediated epithelial-mesenchymal transition and tumor cell growth. , 2010, Cancer letters.

[10]  D. Mcfadden,et al.  Pterostilbene Inhibits Pancreatic Cancer In Vitro , 2010, Journal of Gastrointestinal Surgery.

[11]  Jun Yu,et al.  Warburg effect revisited: an epigenetic link between glycolysis and gastric carcinogenesis , 2010, Oncogene.

[12]  D. Mcfadden,et al.  Pterostilbene inhibits lung cancer through induction of apoptosis. , 2009, The Journal of surgical research.

[13]  J. Schneider,et al.  ASSOCIATION FOR ACADEMIC SURGERY Pterostilbene Inhibits Breast Cancer In Vitro Through Mitochondrial Depolarization and Induction of Caspase-Dependent Apoptosis 1 , 2010 .

[14]  Jun Yu,et al.  Promoter Hypermethylation Mediates Downregulation of Thiamine Receptor SLC19A3 in Gastric Cancer , 2009, Tumor Biology.

[15]  Chi-Tang Ho,et al.  Pterostilbene inhibited tumor invasion via suppressing multiple signal transduction pathways in human hepatocellular carcinoma cells. , 2009, Carcinogenesis.

[16]  J. K. Kundu,et al.  Cancer chemopreventive and therapeutic potential of resveratrol: mechanistic perspectives. , 2008, Cancer letters.

[17]  Chi-Tang Ho,et al.  Pterostilbene induces apoptosis and cell cycle arrest in human gastric carcinoma cells. , 2007, Journal of agricultural and food chemistry.

[18]  J. Brooks,et al.  Resveratrol-Induced Gene Expression Profiles in Human Prostate Cancer Cells , 2005, Cancer Epidemiology Biomarkers & Prevention.

[19]  J. Estrela,et al.  Association between pterostilbene and quercetin inhibits metastatic activity of B16 melanoma. , 2005, Neoplasia.

[20]  J. Russo,et al.  Antiproliferative effect of synthetic resveratrol on human breast epithelial cells. , 1998, International journal of oncology.

[21]  Norman R. Farnsworth,et al.  Cancer Chemopreventive Activity of Resveratrol, a Natural Product Derived from Grapes , 1997, Science.