An all natural immuno-oncology adjuvant

Pterostilbene (trans-3,5-dimethoxy-4-hydroxystilbene), is a dimethylated analog of resveratrol which is found in blueberries [1], and is believed to be one of the active ingredients in ancient Indian Medicine [2]. The pterostilbene molecule is structurally similar to resveratrol, the antioxidant found in red wine that has comparable anti-inflammatory, and anticarcinogenic properties; however, pterostilbene exhibits increased bioavailability due to the presence of two methoxy groups which cause it to exhibit increased lipophilic and oral absorption [3-7]. In animal studies, pterostilbene was shown to have 80% bioavailability compared to 20% for resveratrol making it potentially advantageous as a therapeutic agent [3].

Direct anticancer activity of pterostilbene has been demonstrated in the majority of cancers including: melanoma [8-12], glioma [13-16], ovarian cancer [17, 18], prostate cancer [19-25], pancreatic cancer [26-28], breast cancer [29-41], liver cancer [42-45], colorectal cancer [46-48], and various liquid tumors (leukemias) [49-52]. The anticancer activities of pterostilbene are unique as compared to other agents such as chemotherapeutic agents or kinase inhibitors in that pterostilbene attacks tumors at multiple targets.

For example inhibition of tumor metastasis through suppression of matrix metalloproteases [8], suppression of tumor anti-apoptotic activity through modulation of bcl-2 [9], and nrf2 [12], and suppression of tumor cell cycle progression [53], have all been attributed to pterostilbene. Most interestingly, inhibition of cancer stem cells by pterostilbene administration has been reported [54]. This would conceptually be in line with studies showing pterostilbene inhibition of drug resistant and radiation resistant tumors, which are believed to possess the resistance phenotype due to increased numbers of cancer stem cells [14].

Oxidative stress is a major feature of numerous types of cancer, caused by tumor cells themselves, as well as neutrophils and macrophages responding to the tumor. It is well known that chronic oxidative stress, which correlates to an inflammatory state in the patient, is a major contributor to immune suppression of both innate and adaptive arms of the immune system [55].

PubChem is an open chemistry database at the National Institutes of Health (NIH). They describe pterostilbene as the following:

A naturally-derived stilbenoid structurally related to resveratrol, with potential antioxidant, anti-inflammatory, pro-apoptotic, antineoplastic and cytoprotective activities. Upon administration, pterostilbene exerts its anti-oxidant activity by scavenging reactive oxygen species (ROS), thereby preventing oxidative stress and ROS-induced cell damage. It may also activate the nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated pathway and increase the expression of various antioxidant enzymes, such as superoxide dismutase (SOD). In addition, pterostilbene is able to inhibit inflammation by reducing the expression of various inflammatory mediators, such as interleukin (IL) 1beta, tumor necrosis factor alpha (TNF-a), inducible nitric oxide synthase (iNOS), cyclooxygenases (COX), and nuclear factor kappa B (NF-kB). It also inhibits or prevents the activation of many signaling pathways involved in carcinogenesis, and increases expression of various tumor suppressor genes while decreasing expression of certain tumor promoting genes. It also directly induces apoptosis in tumor cells.

Pharmacology from NCIt
Source: NCIt
Record Name: Pterostilbene
Description: NCI Thesaurus (NCIt) provides reference terminology for many systems. It covers vocabulary for clinical care, translational and basic research, and public information and administrative activities.


1.         McCormack, D. and D. McFadden, A review of pterostilbene antioxidant activity and disease modification.Oxid Med Cell Longev, 2013. 2013: p. 575482.

2.         Paul, B., et al., Occurrence of resveratrol and pterostilbene in age-old darakchasava, an ayurvedic medicine from India.J Ethnopharmacol, 1999. 68(1-3): p. 71-6.

3.         Kapetanovic, I.M., et al., Pharmacokinetics, oral bioavailability, and metabolic profile of resveratrol and its dimethylether analog, pterostilbene, in rats.Cancer Chemother Pharmacol, 2011. 68(3): p. 593-601.

4.         Perecko, T., et al., Molecular targets of the natural antioxidant pterostilbene: effect on protein kinase C, caspase-3 and apoptosis in human neutrophils in vitro.Neuro Endocrinol Lett, 2010. 31 Suppl 2: p. 84-90.

5.         Stivala, L.A., et al., Specific structural determinants are responsible for the antioxidant activity and the cell cycle effects of resveratrol.J Biol Chem, 2001. 276(25): p. 22586-94.

6.         Athar, M., et al., Resveratrol: a review of preclinical studies for human cancer prevention.Toxicol Appl Pharmacol, 2007. 224(3): p. 274-83.

7.         Bishayee, A., Cancer prevention and treatment with resveratrol: from rodent studies to clinical trials.Cancer Prev Res (Phila), 2009. 2(5): p. 409-18.

8.         Ferrer, P., et al., Association between pterostilbene and quercetin inhibits metastatic activity of B16 melanoma.Neoplasia, 2005. 7(1): p. 37-47.

9.         Ferrer, P., et al., Nitric oxide mediates natural polyphenol-induced Bcl-2 down-regulation and activation of cell death in metastatic B16 melanoma.J Biol Chem, 2007. 282(5): p. 2880-90.

10.       Huang, X.Y., S.Z. Zhang, and W.X. Wang, Enhanced antitumor efficacy with combined administration of astragalus and pterostilbene for melanoma.Asian Pac J Cancer Prev, 2014. 15(3): p. 1163-9.

11.       Schneider, J.G., et al., Effects of pterostilbene on melanoma alone and in synergy with inositol hexaphosphate.Am J Surg, 2009. 198(5): p. 679-84.

12.       Benlloch, M., et al., Pterostilbene Decreases the Antioxidant Defenses of Aggressive Cancer Cells In Vivo: A Physiological Glucocorticoids- and Nrf2-Dependent Mechanism.Antioxid Redox Signal, 2016. 24(17): p. 974-90.

13.       Schmidt, L., et al., Comparative drug pair screening across multiple glioblastoma cell lines reveals novel drug-drug interactions.Neuro Oncol, 2013. 15(11): p. 1469-78.

14.       Huynh, T.T., et al., Pterostilbene suppressed irradiation-resistant glioma stem cells by modulating GRP78/miR-205 axis.J Nutr Biochem, 2015. 26(5): p. 466-75.

15.       Schmidt, L., et al., Case-specific potentiation of glioblastoma drugs by pterostilbene.Oncotarget, 2016. 7(45): p. 73200-73215.

16.       Zielinska-Przyjemska, M., et al., The effect of resveratrol, its naturally occurring derivatives and tannic acid on the induction of cell cycle arrest and apoptosis in rat C6 and human T98G glioma cell lines.Toxicol In Vitro, 2017. 43: p. 69-75.

17.       Dong, J., H. Guo, and Y. Chen, Pterostilbene induces apoptosis through caspase activation in ovarian cancer cells.Eur J Gynaecol Oncol, 2016. 37(3): p. 342-7.

18.       Pei, H.L., D.M. Mu, and B. Zhang, Anticancer Activity of Pterostilbene in Human Ovarian Cancer Cell Lines.Med Sci Monit, 2017. 23: p. 3192-3199.

19.       Wang, T.T., et al., Differential effects of resveratrol and its naturally occurring methylether analogs on cell cycle and apoptosis in human androgen-responsive LNCaP cancer cells.Mol Nutr Food Res, 2010. 54(3): p. 335-44.

20.       Lin, V.C., et al., Activation of AMPK by pterostilbene suppresses lipogenesis and cell-cycle progression in p53 positive and negative human prostate cancer cells.J Agric Food Chem, 2012. 60(25): p. 6399-407.

21.       Li, K., et al., Pterostilbene acts through metastasis-associated protein 1 to inhibit tumor growth, progression and metastasis in prostate cancer.PLoS One, 2013. 8(3): p. e57542.

22.       Kumar, A., et al., Epigenetic potential of resveratrol and analogs in preclinical models of prostate cancer.Ann N Y Acad Sci, 2015. 1348(1): p. 1-9.

23.       Dhar, S., et al., Resveratrol and pterostilbene epigenetically restore PTEN expression by targeting oncomiRs of the miR-17 family in prostate cancer.Oncotarget, 2015. 6(29): p. 27214-26.

24.       Dhar, S., et al., Dietary pterostilbene is a novel MTA1-targeted chemopreventive and therapeutic agent in prostate cancer.Oncotarget, 2016. 7(14): p. 18469-84.

25.       Kumar, A., A.M. Rimando, and A.S. Levenson, Resveratrol and pterostilbene as a microRNA-mediated chemopreventive and therapeutic strategy in prostate cancer.Ann N Y Acad Sci, 2017. 1403(1): p. 15-26.

26.       Kostin, S.F., D.E. McDonald, and D.W. McFadden, Inhibitory effects of (-)-epigallocatechin-3-gallate and pterostilbene on pancreatic cancer growth in vitro.J Surg Res, 2012. 177(2): p. 255-62.

27.       McCormack, D.E., et al., Genomic analysis of pterostilbene predicts its antiproliferative effects against pancreatic cancer in vitro and in vivo.J Gastrointest Surg, 2012. 16(6): p. 1136-43.

28.       Mannal, P.W., et al., Pterostilbene inhibits pancreatic cancer in vitro.J Gastrointest Surg, 2010. 14(5): p. 873-9.

29.       Pan, M.H., et al., Suppression of Heregulin-beta1/HER2-Modulated Invasive and Aggressive Phenotype of Breast Carcinoma by Pterostilbene via Inhibition of Matrix Metalloproteinase-9, p38 Kinase Cascade and Akt Activation.Evid Based Complement Alternat Med, 2011. 2011: p. 562187.

30.       Alosi, J.A., et al., Pterostilbene inhibits breast cancer in vitro through mitochondrial depolarization and induction of caspase-dependent apoptosis.J Surg Res, 2010. 161(2): p. 195-201.

31.       Mannal, P., D. McDonald, and D. McFadden,Pterostilbene and tamoxifen show an additive effect against breast cancer in vitro.Am J Surg, 2010. 200(5): p. 577-80.

32.       McCormack, D., et al., The antiproliferative effects of pterostilbene on breast cancer in vitro are via inhibition of constitutive and leptin-induced Janus kinase/signal transducer and activator of transcription activation.Am J Surg, 2011. 202(5): p. 541-4.

33.       Chakraborty, A., et al., Long term induction by pterostilbene results in autophagy and cellular differentiation in MCF-7 cells via ROS dependent pathway.Mol Cell Endocrinol, 2012. 355(1): p. 25-40.

34.       Wang, Y., et al., Pterostilbene simultaneously induces apoptosis, cell cycle arrest and cyto-protective autophagy in breast cancer cells.Am J Transl Res, 2012. 4(1): p. 44-51.

35.       Moon, D., et al., Pterostilbene induces mitochondrially derived apoptosis in breast cancer cells in vitro.J Surg Res, 2013. 180(2): p. 208-15.

36.       Hong, B.H., et al., Invadopodia-associated proteins blockade as a novel mechanism for 6-shogaol and pterostilbene to reduce breast cancer cell motility and invasion.Mol Nutr Food Res, 2013. 57(5): p. 886-95.

37.       Pan, C., et al., Estrogen receptor-alpha36 is involved in pterostilbene-induced apoptosis and anti-proliferation in in vitro and in vivo breast cancer.PLoS One, 2014. 9(8): p. e104459.

38.       Su, C.M., et al., Pterostilbene inhibits triple-negative breast cancer metastasis via inducing microRNA-205 expression and negatively modulates epithelial-to-mesenchymal transition.J Nutr Biochem, 2015. 26(6): p. 675-85.

39.       Kala, R., et al., Epigenetic-based combinatorial resveratrol and pterostilbene alters DNA damage response by affecting SIRT1 and DNMT enzyme expression, including SIRT1-dependent gamma-H2AX and telomerase regulation in triple-negative breast cancer.BMC Cancer, 2015. 15: p. 672.

40.       Kala, R. and T.O. Tollefsbol, A Novel Combinatorial Epigenetic Therapy Using Resveratrol and Pterostilbene for Restoring Estrogen Receptor-alpha (ERalpha) Expression in ERalpha-Negative Breast Cancer Cells.PLoS One, 2016. 11(5): p. e0155057.

41.       Lubecka, K., et al., Stilbenoids remodel the DNA methylation patterns in breast cancer cells and inhibit oncogenic NOTCH signaling through epigenetic regulation of MAML2 transcriptional activity.Carcinogenesis, 2016. 37(7): p. 656-68.

42.       Pan, M.H., et al., Pterostilbene inhibited tumor invasion via suppressing multiple signal transduction pathways in human hepatocellular carcinoma cells.Carcinogenesis, 2009. 30(7): p. 1234-42.

43.       Huang, C.S., et al., Long-term ethanol exposure-induced hepatocellular carcinoma cell migration and invasion through lysyl oxidase activation are attenuated by combined treatment with pterostilbene and curcumin analogues.J Agric Food Chem, 2013. 61(18): p. 4326-35.

44.       Lombardi, G., et al., In Vitro Safety/Protection Assessment of Resveratrol and Pterostilbene in a Human Hepatoma Cell Line (HepG2).Nat Prod Commun, 2015. 10(8): p. 1403-8.

45.       Guo, L., et al., Pterostilbene inhibits hepatocellular carcinoma through p53/SOD2/ROS-mediated mitochondrial apoptosis.Oncol Rep, 2016. 36(6): p. 3233-3240.

46.       Priego, S., et al., Natural polyphenols facilitate elimination of HT-29 colorectal cancer xenografts by chemoradiotherapy: a Bcl-2- and superoxide dismutase 2-dependent mechanism.Mol Cancer Ther, 2008. 7(10): p. 3330-42.

47.       Paul, S., et al., Anti-inflammatory action of pterostilbene is mediated through the p38 mitogen-activated protein kinase pathway in colon cancer cells.Cancer Prev Res (Phila), 2009. 2(7): p. 650-7.

48.       Nutakul, W., et al., Inhibitory effects of resveratrol and pterostilbene on human colon cancer cells: a side-by-side comparison.J Agric Food Chem, 2011. 59(20): p. 10964-70.

49.       Tolomeo, M., et al., Pterostilbene and 3′-hydroxypterostilbene are effective apoptosis-inducing agents in MDR and BCR-ABL-expressing leukemia cells.Int J Biochem Cell Biol, 2005. 37(8): p. 1709-26.

50.       Roslie, H., et al., 3,5-dibenzyloxy-4′-hydroxystilbene induces early caspase-9 activation during apoptosis in human K562 chronic myelogenous leukemia cells.J Toxicol Sci, 2012. 37(1): p. 13-21.

51.       Siedlecka-Kroplewska, K., et al., Pterostilbene induces cell cycle arrest and apoptosis in MOLT4 human leukemia cells.Folia Histochem Cytobiol, 2012. 50(4): p. 574-80.

52.       Siedlecka-Kroplewska, K., et al., Pterostilbene induces accumulation of autophagic vacuoles followed by cell death in HL60 human leukemia cells.J Physiol Pharmacol, 2013. 64(5): p. 545-56.

53.       Wen, W., et al., Pterostilbene Suppresses Ovarian Cancer Growth via Induction of Apoptosis and Blockade of Cell Cycle Progression Involving Inhibition of the STAT3 Pathway.Int J Mol Sci, 2018. 19(7).

54.       Zhang, L., et al., Targeting cancer stem cells and signaling pathways by resveratrol and pterostilbene.Biofactors, 2018. 44(1): p. 61-68.

55.       Ichim, T.E., et al., Intravenous ascorbic acid to prevent and treat cancer-associated sepsis?J Transl Med, 2011. 9: p. 25.

56.       Mhatre, S., et al., Rapid flow cytometry based cytotoxicity assay for evaluation of NK cell function.Indian J Exp Biol, 2014. 52(10): p. 983-8.