Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
권호 표지
DOI QR코드

DOI QR Code

Cancer Chemopreventive Potential of Procyanidin

  • Lee, Yongkyu (Department of Food Science & Nutrition, Dongseo University)
  • Received : 2017.08.28
  • Accepted : 2017.09.27
  • Published : 2017.10.15
Download PDF
⟨ Previous Next ⟩

Abstract

Chemoprevention entails the use of synthetic agents or naturally occurring dietary phytochemicals to prevent cancer development and progression. One promising chemopreventive agent, procyanidin, is a naturally occurring polyphenol that exhibits beneficial health effects including anti-inflammatory, antiproliferative, and antitumor activities. Currently, many preclinical reports suggest procyanidin as a promising lead compound for cancer prevention and treatment. As a potential anticancer agent, procyanidin has been shown to inhibit the proliferation of various cancer cells in "in vitro and in vivo". Procyanidin has numerous targets, many of which are components of intracellular signaling pathways, including proinflammatory mediators, regulators of cell survival and apoptosis, and angiogenic and metastatic mediators, and modulates a set of upstream kinases, transcription factors, and their regulators. Although remarkable progress characterizing the molecular mechanisms and targets underlying the anticancer properties of procyanidin has been made in the past decade, the chemopreventive targets or biomarkers of procyanidin action have not been completely elucidated. This review focuses on the apoptosis and tumor inhibitory effects of procyanidin with respect to its bioavailability.

Keywords

References

  1. Doll, R. and Peto, R. (1981) The causes of cancer, quantitative estimates of risks of cancer in the United States today. J. Natl. Cancer Inst., 66, 1191-1308.
  2. Riboli, E. and Norat, T. (2003) Epidemiologic evidence of the protective effect of fruit and vegetables on cancer risk. Am. J. Clin. Nutr., 78, 559S-569S. https://doi.org/10.1093/ajcn/78.3.559S
  3. Willet, W.C., Stampfer, M.J., Colditz, G.A., Rosner, B.A. and Speizer, F.E. (1990) Relation of meat, fat, and fiber intake to the risk of colon cancer in a prospective study among women. N. Engl. J. Med., 323, 1664-1672. https://doi.org/10.1056/NEJM199012133232404
  4. Glade, M.J. (1997) Food, nutrition, and the prevention of cancer, a global perspective. American institute for cancer research/World cancer research fund, American Institute for Cancer Research. Nutrition, 15, 523-526.
  5. Zhao, J., Wang, J., Chen, Y. and Agarwal, R. (1999) Antitumor-promoting activity of a polyphenolic fraction isolated from grape seeds in the mouse skin two-stage initiation-promotion protocol and identification of procyanidin $B_5$-3'-gallate as the most effective antioxidant constituent. Carcinogenesis, 20, 1737-1745. https://doi.org/10.1093/carcin/20.9.1737
  6. Matito, C., Mastorakou, F., Centelles, J.J., Torres, J.L. and Cascante, M. (2003) Antiproliferative effect of antioxidant polyphenols from grape in murine Hepa-1c1c7. Eur. J. Nutr., 42, 43-49. https://doi.org/10.1007/s00394-003-0398-2
  7. Torres, J.L., Varela, B., Garcia, M.T., Carilla, J., Matito, C., Centelles, J.J., Cascante, M., Sort, X. and Bobet, R. (2002) Valorization of grape (Vitis vinifera) byproducts. Antioxidant and biological properties of polyphenolic fractions differing in procyanidin composition and flavonol content. J. Agric. Food Chem., 50, 7548-7555. https://doi.org/10.1021/jf025868i
  8. Avelar, M.M. and Gouvea, C.M. (2012) Procyanidin $B_2$ cytotoxicity to MCF-7 human breast adenocarcinoma cells. Indian J. Pharm. Sci., 74, 351-355. https://doi.org/10.4103/0250-474X.107070
  9. Agarwal, C., Sharma, Y., Zhao, J. and Agarwal, R. (2000) A polyphenolic fraction from grape seeds causes irreversible growth inhibition of breast carcinoma MDA-MB468 cells by inhibiting mitogen-activated protein kinases activation and inducing $G_1$ arrest and differentiation. Clin. Cancer Res., 6, 2921-2930.
  10. Ye, X., Krohn, R.L., Liu, W., Joshi, S.S., Kuszynski, C.A., McGinn, T.R., Bagchi, M., Preuss, H.G., Stohs, S.J. and Bagchi, D. (1999) The cytotoxic effects of a novel IH636 grape seed proanthocyanidin extract on cultured human cancer cells. Mol. Cell. Biochem., 196, 99-108. https://doi.org/10.1023/A:1006926414683
  11. Chatelain, K., Phippen, S., McCabe, J., Teeters, C.A., O'Malley, S. and Kingsley, K. (2011) Cranberry and grape seed extracts inhibit the proliferative phenotype of oral squamous cell carcinomas. Evid. Based Complement. Alternat. Med., 2011, 467691.
  12. Tyagi, A., Agarwal, R. and Agarwal, C. (2003) Grape seed extract inhibits EGF-induced and constitutively active mitogenic signaling but activates JNK in human prostate carcinoma DU145 cells: possible role in antiproliferation and apoptosis. Oncogene, 22, 1302-1316. https://doi.org/10.1038/sj.onc.1206265
  13. Agarwal, C., Singh, R.P. and Agarwal, R. (2002) Grape seed extract induces apoptotic death of human prostate carcinoma DU145 cells via caspases activation accompanied by dissipation of mitochondrial membrane potential and cytochrome c release. Carcinogenesis, 23, 1869-1876. https://doi.org/10.1093/carcin/23.11.1869
  14. Singh, R.P., Tyagi, A.K., Dhanalakshmi, S., Agarwal, R. and Agarwal, C. (2004) Grape seed extract inhibits advanced human prostate tumor growth and angiogenesis and upregulates insulin-like growth factor binding protein-3. Int. J. Cancer, 108, 733-740. https://doi.org/10.1002/ijc.11620
  15. Kaur, M., Agarwal, R. and Agarwal, C. (2006) Grape seed extract induces anoikis and caspase-mediated apoptosis in human prostate carcinoma LNCaP cells: possible role of ataxia telangiectasia mutated-p53 activation. Mol. Cancer Ther., 5, 1265-1274.
  16. Liu, J., Zhang, W.Y., Kong, Z.H. and Ding, D.G. (2016) Induction of cell cycle arrest and apoptosis by grape seed procyanidin extract in human bladder cancer BIU87 cells. Eur. Rev. Med. Pharmacol. Sci., 20, 3282-3291.
  17. Engelbrecht, A.M., Mattheyse, M., Ellis, B., Loos, B., Thomas, M., Smith, R., Peters, S., Smith, C. and Myburgh, K. (2007) Proanthocyanidin from grape seeds inactivates the PI3-kinase/PKB pathway and induces apoptosis in a colon cancer cell line. Cancer Lett., 258, 144-153. https://doi.org/10.1016/j.canlet.2007.08.020
  18. Kaur, M., Mandair, R., Agarwal, R. and Agarwal, C. (2008) Grape seed extract induces cell cycle arrest and apoptosis in human colon carcinoma cells. Nutr. Cancer, 60 Suppl 1, 2-11. https://doi.org/10.1080/01635580802381295
  19. Kaur, M., Singh, R.P. and Gu, M. (2006) Grape seed extract inhibits in vitro and in vivo growth of human colorectal carcinoma cells. Clin. Cancer Res., 12, 6194-6202. https://doi.org/10.1158/1078-0432.CCR-06-1465
  20. Owczarek, K., Hrabec, E., Fichna, J., Sosnowska, D., Koziolkiewicz, M., Szymanski, J. and Lewandowska, U. (2017) Flavanols from Japanese quince (Chaenomeles japonica) fruit suppress expression of cyclooxygenase-2, metalloproteinase-9, and nuclear factor-${\kappa}B$ in human colon cancer cells. Acta Biochim. Pol., 64, 567-576. https://doi.org/10.18388/abp.2017_1599
  21. Hsu, C.P., Lin, Y.H., Chou, C.C., Zhou, S.P., Hsu, Y.C., Liu, C.L., Ku, F.M. and Chung, Y.C. (2009) Mechanisms of grape seed procyanidin-induced apoptosis in colorectal carcinoma cells. Anticancer Res., 29, 283-289.
  22. Dinicola, S., Cucina, A., Pasqualato, A., D'Anselmi, F., Proietti, S., Lisi, E., Pasqua, G., Antonacci, D. and Bizzarri, M. (2012) Antiproliferative and apoptotic effects triggered by Grape Seed Extract (GSE) versus epigallocatechin and procyanidins on colon cancer cell lines. Int. J. Mol. Sci., 13, 651-664. https://doi.org/10.3390/ijms13010651
  23. Gorlach, S., Wagner, W., Podsędek, A., Szewczyk, K., Koziolkiewicz, M. and Dastych, J. (2011) Procyanidins from Japanese quince (Chaenomeles japonica) fruit induce apoptosis in human colon cancer Caco-2 cells in a degree of polymerization-dependent manner. Natur. Cancer, 63, 1348-1360. https://doi.org/10.1080/01635581.2011.608480
  24. Yamakoshi, J., Saito, M., Kataoka, S. and Kikuchi, M. (2002) Safety evaluation of proanthocyanidin-rich extract from grape seeds. Food Chem. Toxicol., 40, 599-607. https://doi.org/10.1016/S0278-6915(02)00006-6
  25. Mittal, A., Elmets, C.A. and Katiyar, S.K. (2003) Dietary feeding of proanthocyanidins from grape seeds prevents photocarcinogenesis in SKH-1 hairless mice: relationship to decreased fat and lipid peroxidation. Carcinogenesis, 24, 1379-1388. https://doi.org/10.1093/carcin/bgg095
  26. Engelbrecht, A.M., Mattheyse, M., Ellis, B., Loos, B., Thomas, M., Smith, R., Peters, S., Smith, C. and Myburgh, K. (2007) Proanthocyanidin from grape seeds inactivates the PI3-kinase/PKB pathway and induces apoptosis in a colon cancer cell line. Cancer Lett., 258, 144-153. https://doi.org/10.1016/j.canlet.2007.08.020
  27. Dai, J. and Mumper, R.J. (2010) Plant phenolics: extraction, analysis and their antioxidant and anticancer properties. Molecules, 15, 7313-7352. https://doi.org/10.3390/molecules15107313
  28. Martin-Cordero, C., Leon-Gonzalez, A.J., Calderon-Montano, J.M., Burgos-Moron, E. and Lopez-Lazaro, M. (2012) Pro-oxidant natural products as anticancer agents. Curr. Drug Targets, 13, 1006-1028. https://doi.org/10.2174/138945012802009044
  29. Xu, B. and Chang, S.K. (2012) Comparative study on antiproliferation properties and cellular antioxidant activities of commonly consumed food legumes against nine human cancer cell lines. Food Chem., 134, 1287-1296. https://doi.org/10.1016/j.foodchem.2012.02.212
  30. Li, S., Xu, M., Niu, Q., Xu, S., Din, Y., Yan, Y., Guo, S. and Li, F. (2015) Efficacy of procyanidins against in vivo cellular oxidative damage: a systematic review and meta-analysis. PLoS ONE, 10, e0139455. https://doi.org/10.1371/journal.pone.0139455
  31. Wallace, T.C. and Giusti, M.M. (2010) Evaluation of parameters that affect the 4-dimethylaminocinnamaldehyde assay for flavanols and proanthocyanidins. J. Food Sci., 75, C619-C625. https://doi.org/10.1111/j.1750-3841.2010.01734.x
  32. Pierini, R., Kroon, P.A., Guyot, S., Ivory, K., Johnson, I.T. and Belshaw, N.J. (2008) Procyanidin effects on oesophageal adenocarcinoma cells strongly depend on flavan-3-ol degree of polymerization. Mol. Nutr. Food Res., 52, 1399-1407. https://doi.org/10.1002/mnfr.200700513
  33. Shoji, T., Masumoto, S., Moriichi, N., Kobori, M., Kanda, T., Shinmoto, H. and Tsushida, T. (2005) Procyanidin trimers to pentamers fractionated from apple inhibit melanogenesis in B16 mouse melanoma cells. J. Agric. Food Chem., 53, 6105-6111. https://doi.org/10.1021/jf050418m
  34. Tyagi, A., Raina, K., Shrestha, S.P., Miller, B., Thompson, J.A., Wempe, M.F., Agarwal, R. and Agarwal, C. (2014) Procyanidin B2 3,3''-di-O-gallate, a biologically active constituent of grape seed extract, induces apoptosis in human prostate cancer cells via targeting NF-${\kappa}B$, Stat3 and AP1 transcription factors. Nutr. Cancer, 66, 736-746. https://doi.org/10.1080/01635581.2013.783602
  35. Mackenzie, G.G., Adamo, A.M., Decker, N.P. and Oteiza, P.I. (2008) Dimeric procyanidin $B_2$ inhibits constitutively active NF-${\kappa}B$ in Hodgkin's lymphoma cells independently of the presence of $I{\kappa}B$ mutations. Biochem. Pharmacol., 75, 1461-1471. https://doi.org/10.1016/j.bcp.2007.12.013
  36. Fu, M., Wang, C., Wang, J., Zhang, X., Sakamaki, T., Yeung, Y.G., Chang, C., Hopp, T., Fuqua, S.A., Jaffray, E., Hay, R.T., Palvimo, J.J., Janne, O.A. and Pestell, R.G. (2002) Androgen receptor acetylation governs trans activation and MEKK1-induced apoptosis without affecting in vitro sumoylation and trans-repression function. Mol. Cell. Biol., 22, 3373-3388. https://doi.org/10.1128/MCB.22.10.3373-3388.2002
  37. Shiota, M., Yokomizo, A., Masubuchi, D., Tada, Y., Inokuchi, J, Eto, M., Uchiumi, T., Fujimoto, N. and Naito, S. (2010) Tip60 promotes prostate cancer cell proliferation by translocation of androgen receptor into the nucleus. Prostate, 70, 540-554.
  38. Fu, M., Rao, M., Wang, C., Sakamaki, T., Wang, J., Di Vizio, D., Zhang, X., Albanese, C., Balk, S., Chang, C., Fan, S., Rosen, E., Palvimo, J.J., Janne, O.A., Muratoglu, S., Avantaggiati, M.L. and Pestell, R.G. (2003) Acetylation of androgen receptor enhances coactivator binding and promotes prostate cancer cell growth. Mol. Cell. Biol., 23, 8563-8575. https://doi.org/10.1128/MCB.23.23.8563-8575.2003
  39. Choi, K.C., Park, S., Lim, B.J., Seong, A.R., Lee, Y.H., Shiota, M., Yokomizo, A., Naito, S., Na, Y. and Yoon, H.G. (2011) Procyanidin B3, an inhibitor of histone acetyltransferase, enhances the action of antagonist for prostate cancer cells via inhibition of p300-dependent acetylation of androgen receptor. Biochem. J., 433, 235-244. https://doi.org/10.1042/BJ20100980
  40. Suzuki, T., Tanaka, R., Hamada, S., Nakagawa, H. and Miyata, N. (2010) Design, synthesis, inhibitory activity, and binding mode study of novel DNA methyltransferase 1 inhibitors. Bioorg. Med. Chem. Lett., 20, 1124-1127. https://doi.org/10.1016/j.bmcl.2009.12.016
  41. Shilpi, A., Parbin, S., Sengupta, D., Kar, S., Deb, M., Rath, S.K., Pradhan, N., Rakshit, M. and Patra, S.K. (2015) Mechanisms of DNA methyltransferase-inhibitor interactions: Procyanidin B2 shows new promise for therapeutic intervention of cancer. Chem. Biol. Interact., 233, 122-138. https://doi.org/10.1016/j.cbi.2015.03.022
  42. Mao, J.T., Smoake, J., Park, H.K., Lu, Q.Y. and Xue, B. (2016) Grape seed procyanidin extract mediates antineoplastic effects against lung cancer via modulations of prostacyclin and 15-HETE eicosanoid pathways. Cancer Prev. Res. (Phila), 9, 925-932. https://doi.org/10.1158/1940-6207.CAPR-16-0122
  43. Hussain, S.P. and Harris, C.C. (2007) Inflammation and cancer: an ancient link with novel potentials. Int. J. Cancer, 121, 2373-2380. https://doi.org/10.1002/ijc.23173
  44. Meeran, S.M. and Katiyar, S.K. (2008) Proanthocyanidins inhibit mitogenic and survival-signaling in vitro and tumor growth in vivo. Front. Biosci., 13, 887-897. https://doi.org/10.2741/2729
  45. Chung, Y.C., Huang, C.C., Chen, C.H., Chiang, H.C., Chen, K.B., Chen, Y.J., Liu, C.L., Chuang, L.T., Liu, M. and Hsu, C.P. (2012) Grape-seed procyanidins inhibit the in vitro growth and invasion of pancreatic carcinoma cells. Pancreas, 41, 447-454. https://doi.org/10.1097/MPA.0b013e318229da41
  46. Taparia, S.S. and Khanna, A. (2016) Effect of procyanidinrich extract from natural cocoa powder on cellular viability, cell cycle progression, and chemoresistance in human epithelial ovarian carcinoma cell lines. Pharmacogn. Mag., 12, S109-S115.
  47. Meeran, S.M. and Katiyar, S.K. (2007) Grape seed proanthocyanidins promote apoptosis in human epidermoid carcinoma A431 cells through alterations in Cdki-Cdk-cyclin cascade, and caspase-3 activation via loss of mitochondrial membrane potential. Exp. Dermatol., 16, 405-415. https://doi.org/10.1111/j.1600-0625.2007.00542.x
  48. Pierini, R., Kroon, P.A., Guyot, S., Johnson, I.T. and Belshaw, N.J. (2008) The procyanidin-mediated induction of apoptosis and cell-cycle arrest in esophageal adenocarcinoma cells is not dependent on p21 (Cip1/WAF1). Cancer Lett., 270, 234-241. https://doi.org/10.1016/j.canlet.2008.05.004
  49. Malumbres, M. and Barbacid, M. (2001) To cycle or not to cycle: a critical decision in cancer. Nat. Rev. Cancer, 1, 222-231. https://doi.org/10.1038/35106065
  50. Sherr, C.J. (2000) Cell cycle control and cancer. Harvey Lect., 96, 73-92.
  51. Taparia, S.S. and Khanna, A. (2016) Procyanidin-rich extract of natural cocoa powder causes ROS-mediated caspase-3 dependent apoptosis and reduction of pro-MMP-2 in epithelial ovarian carcinoma cell lines. Biomed. Pharmacother., 83, 130-140. https://doi.org/10.1016/j.biopha.2016.06.019
  52. Connor, C.A., Adriaens, M., Pierini, R., Johnson, I.T. and Belshaw, N.J. (2014) Procyanidin induces apoptosis of esophageal adenocarcinoma cells via JNK activation of c-Jun. Nutr. Cancer, 66, 335-341. https://doi.org/10.1080/01635581.2014.868914
  53. Cedo, L., Castell-Auvi, A., Pallares, V., Macia, A., Blay, M., Ardevol, A., Motilva, M.J. and Pinent, M. (2014) Gallic acid is an active component for the anticarcinogenic action of grape seed procyanidins in pancreatic cancer cells. Nutr. Cancer, 66, 88-96. https://doi.org/10.1080/01635581.2014.851714
  54. Lewandowska, U., Szewczyk, K., Owczarek, K., Hrabec, Z., Podsędek, A., Sosnowska, D. and Hrabec, E. (2013) Procyanidins from evening primrose (Oenothera paradoxa) defatted seeds inhibit invasiveness of breast cancer cells and modulate the expression of selected genes involved in angiogenesis, metastasis, and apoptosis. Nutr. Cancer, 65, 1219-1231. https://doi.org/10.1080/01635581.2013.830314
  55. Lin, Y.S., Chen, S.F., Liu, C.L. and Nieh, S.J. (2012) The chemoadjuvant potential of grape seed procyanidins on p53-related cell death in oral cancer cells. J. Oral Pathol. Med., 41, 322-331. https://doi.org/10.1111/j.1600-0714.2011.01103.x
  56. Callejas, N.A., Casado, M., Bosca, L. and Martin-Sanz, P. (1999) Requirement of nuclear factor ${\kappa}B$ for the constitutive expression of nitric oxide synthase-2 and cyclooxygenase-2 in rat trophoblasts. J. Cell Sci., 112, 3147-3155.
  57. Carpenter, C.L. and Cantley, L.C. (1996) Phosphoinositide kinases. Curr. Opin. Cell Biol., 8, 153-158. https://doi.org/10.1016/S0955-0674(96)80060-3
  58. Romashkova, J.A. and Makarov, S.S. (1999) NF-${\kappa}B$ is a target of AKT in anti-apoptotic PDGF signalling. Nature, 401, 86-90. https://doi.org/10.1038/43474
  59. Stambolic, V., Suzuki, A., de la Pompa, J.L., Brothers, G.M., Mirtsos, C., Sasaki, T., Ruland, J., Penninger, J.M., Siderovski, D.P. and Mak, T.W. (1998) Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN. Cell, 95, 29-39. https://doi.org/10.1016/S0092-8674(00)81780-8
  60. Wu, X., Senechal, K., Neshat, M.S., Whang, Y.E. and Sawers, C.L. (1998) The PTEN/MMAC1 tumor suppressor phosphatase functions as a negative regulator of the phosphoinositide 3-kinase/Akt pathway. Proc. Natl. Acad. Sci. U.S.A., 95, 15587-15591. https://doi.org/10.1073/pnas.95.26.15587
  61. Mao, J.T., Xue, B., Smoake, J., Lu, Q.Y., Park, H., Henning, S.M., Burns, W., Bernabei, A., Elashoff, D., Serio, K.J. and Massie, L. (2016) MicroRNA-19a/b mediates grape seed procyanidin extract-induced anti-neoplastic effects against lung cancer. J. Nutr. Biochem., 34, 118-125. https://doi.org/10.1016/j.jnutbio.2016.05.003
  62. Ohnuma, T., Anzai, E., Suzuki, Y., Shimoda, M., Saito, S., Nishiyama, T., Ogura, K. and Hiratsuka, A. (2015) Selective antagonization of activated Nrf2 and inhibition of cancer cell proliferation by procyanidins from Cinnamomi Cortex extract. Arch. Biochem. Biophys., 585, 17-24. https://doi.org/10.1016/j.abb.2015.09.007
  63. Singh, A., Misra, V., Thimmulappa, R.K., Lee, H., Ames, S., Hoque, M.O., Herman, J.G., Baylin, S.B., Sidransk, D., Gabrielson, E., Brock, M.V. and Biswal, S. (2006) Dysfunctional KEAP1-NRF2 interaction in non-small-cell lung cancer, PLoS Med., 3, e420. https://doi.org/10.1371/journal.pmed.0030420
  64. Wang, R., An, J., Ji, F., Jiao, H., Sun, H. and Zhou, D. (2008) Hypermethylation of the Keap1 gene in human lung cancer cell lines and lung cancer tissues. Biochem. Biophys. Res. Commun., 373, 151-154. https://doi.org/10.1016/j.bbrc.2008.06.004
  65. Shibata, T. Ohta, T., Tong, K.I., Kokubu, A., Odogawa, R., Tsuta, K., Asamura, H., Yamamoto, M. and Hirohashi, S. (2008) Cancer related mutations in NRF2 impair its recognition by Keap1-Cul3 E3 ligase and promote malignancy. Proc. Natl. Acad. Sci. U.S.A., 105, 13568-13573. https://doi.org/10.1073/pnas.0806268105
  66. Zhang, P., Singh, A., Yegnasubramanian, S., Esopi, D., Kombairaju, P., Bodas, M., Wu, H., Bova, S.G. and Biswal, S. (2010) Loss of Kelch-like ECH-associated protein 1 function in prostate cancer cells causes chemoresistance and radioresistance and promotes tumor growth. Mol. Cancer Ther., 9, 336-346. https://doi.org/10.1158/1535-7163.MCT-09-0589
  67. Kang, K.A. and Hyun, J.W. (2017) Oxidative stress, Nrf2, and epigenetic modification contribute to anticancer drug resistance. Toxicol. Res., 33, 1-5. https://doi.org/10.5487/TR.2017.33.1.001
  68. Gu, L., Dagvadorj, A., Lutz, J., Leiby, B., Bonuccelli, G., Lisanti, M.P., Addya, S., Fortina, P., Dasgupta, A., Hyslop, T., Bubendorf, L. and Nevalainen, M.T. (2010) Transcription factor Stat3 stimulates metastatic behavior of human prostate cancer cells in vivo, whereas Stat5b has a preferential role in the promotion of prostate cancer cell viability and tumor growth. Am. J. Pathol., 176, 1959-1972. https://doi.org/10.2353/ajpath.2010.090653
  69. Ouyang, X., Jessen, W.J., Al-Ahmadie, H., Serio, A.M., Lin, Y., Shih, W.J., Reuter, V.E., Scardino, P.T., Shen, M.M., Aronow, B.J., Vickers, A.J., Gerald, W.L. and Abate-Shen, C. (2008) Activator protein-1 transcription factors are associated with progression and recurrence of prostate cancer. Cancer Res., 68, 2132-2144. https://doi.org/10.1158/0008-5472.CAN-07-6055
  70. Raina, K., Agarwal, C. and Agarwal, R. (2013) Effect of silibinin in human colorectal cancer cells: targeting the activation of NF-${\kappa}B$ signaling. Mol. Carcinog., 52, 195-206. https://doi.org/10.1002/mc.21843
  71. Sun, M., Liu, C., Nadiminty, N., Lou, W., Zhu, Y., Yang, J., Evans, C.P., Zhou, Q. and Gao A.C. (2012) Inhibition of Stat3 activation by sanguinarine suppresses prostate cancer cell growth and invasion. Prostate, 72, 82-89. https://doi.org/10.1002/pros.21409
  72. Agarwal, C., Veluri, R., Kaur, M., Chou, S.C., Thompson, J.A. and Agarwal, R. (2007) Fractionation of high molecular weight tannins in grape seed extract and identification of procyanidin B2-3,3'-di-O-gallate as a major active constituent causing growth inhibition and apoptotic death of DU145 human prostate carcinoma cells. Carcinogenesis, 28, 1478-1484. https://doi.org/10.1093/carcin/bgm045
  73. Wang, K., Brems, J.J., Gamelli, R.L. and Holterman, A.X. (2010) Survivin signaling is regulated through nuclear factor-${\kappa}B$ pathway during glycochenodeoxycholate-induced hepatocyte apoptosis. Biochim. Biophys. Acta, 1803, 1368-1375. https://doi.org/10.1016/j.bbamcr.2010.08.008
  74. Katiyar, S.K. (2006) Matrix metalloproteinases in cancer metastasis: molecular targets for prostate cancer prevention by green tea polyphenols and grape seed proanthocyanidins. Endocr. Metab. Immune Disord. Drug Targets, 6, 17-24. https://doi.org/10.2174/187153006776056648
  75. La, V.D., Bergeron, C., Gafner, S. and Grenier, D. (2009) Grape seed extract suppresses lipopolysaccharide-induced matrix metalloproteinase (MMP) secretion by macrophages and inhibits human MMP-1 and -9 activities. J. Periodontol., 80, 1875-1882. https://doi.org/10.1902/jop.2009.090251
  76. Agarwal, C., Singh, R.P., Dhanalakshmi, S. and Agarwal, R. (2004) Anti-angiogenic efficacy of grape seed extract in endothelial cells. Oncol. Rep., 11, 681-685.
  77. Dinicola, S., Pasqualato, A., Cucina, A., Coluccia, P., Ferranti, F., Canipari, R., Catizone, A., Proietti, S., D'Anselmi, F., Ricci, G., Palombo, A. and Bizzarri, M. (2014) Grape seed extract suppresses MDA-MB231 breast cancer cell migration and invasion. Eur. J. Nutr., 53, 421-431. https://doi.org/10.1007/s00394-013-0542-6
  78. Wu, D.C., Li, S., Yang, D.Q. and Cui, Y.Y. (2011) Effects of Pinus massoniana bark extract on the adhesion and migration capabilities of HeLa cells. Fitoterapia, 82, 1202-1205. https://doi.org/10.1016/j.fitote.2011.08.008
  79. Kang, N.J., Lee, K.W., Lee, D.E., Rogozin, E.A., Bode, A.M., Lee., H.J. and Dong, Z. (2008) Cocoa procyanidins suppress transformation by inhibiting mitogen-activated protein kinase kinase. J. Biol. Chem., 283, 20664-20673. https://doi.org/10.1074/jbc.M800263200
  80. Feng, L.L., Liu, B.X., Zhong, J.Y., Sun, L.B. and Yu, H.S. (2014) Effect of grape procyanidins on tumor angiogenesis in liver cancer xenograft models. Asian Pac. J. Cancer Prev., 15, 737-741. https://doi.org/10.7314/APJCP.2014.15.2.737
  81. Januchowski, R., Wojtowicz, K., Sujka-Kordowska, P., Andrzejewska, M. and Zabel, M. (2013) MDR gene expression analysis of six drug-resistant ovarian cancer cell lines. Biomed. Res. Int., 2013, 241763.
  82. He, L., Zhao, C., Yan, M., Zhang, L.Y. and Xia, Y.Z. (2009) Inhibition of P-glycoprotein function by procyanidine on blood-brain barrier. Phytother. Res., 23, 933-937. https://doi.org/10.1002/ptr.2781
  83. Zhao, B.X., Sun, Y.B., Wang, S.Q., Duan, L., Huo, Q.L., Ren, F. and Li, G.F. (2013) Grape seed procyanidin reversal of pglycoprotein associated multi-drug resistance via down-regulation of NF-${\kappa}B$ and MAPK/ERK mediated YB-1 activity in A2780/T cells. PLoS ONE, 8, e71071. https://doi.org/10.1371/journal.pone.0071071
  84. Ohnuma, T., Matsumoto, T., Itoi, A., Kawana, A., Nishiyama, T., Ogura, K. and Hiratsuka, A. (2011) Enhanced sensitivity of A549 cells to the cytotoxic action of anticancer drugs via suppression of Nrf2 by procyanidins from Cinnamomi Cortex extract. Biochem. Biophys. Res. Commun., 413, 623-629. https://doi.org/10.1016/j.bbrc.2011.09.014
  85. Zhu, Q.Y., Holt, R.R., Lazarus, S.A., Ensunsa, J.L., Hammerstone, J.F., Schmitz, H.H. and Keen, C.L. (2002) Stability of the flavan-3-ols epicatechin and catechin and related dimeric procyanidins derived from cocoa. J. Agric. Food Chem., 50, 1700-1705. https://doi.org/10.1021/jf011228o
  86. Yoshino, K., Suzuki, M., Sasaki, K., Miyase, T. and Sano, M. (1999) Formation of antioxidants from (-)-epigallocatechin gallate in mild alkaline fluids, such as authentic intestinal juice and mouse plasma. J. Nutr. Biochem., 10, 223-229. https://doi.org/10.1016/S0955-2863(98)00103-X
  87. Zhu, Q.Y., Zhang, A., Tsang, D., Huang, Y. and Chen, Z.-Y. (1997) Stability of green tea catechins. J. Agric. Food Chem., 45, 4624-4628. https://doi.org/10.1021/jf9706080
  88. Serra, A., Macia, A., Romero, M.P., Valls, J., Blade, C., Arola, L. and Motilva, M.J. (2010) Bioavailability of procyanidin dimers and trimers and matrix food effects in in vitro and in vivo models. Br. J. Nutr., 103, 944-952. https://doi.org/10.1017/S0007114509992741
  89. Spencer, J.P., Chaudry, F., Pannala, A.S., Srai, S.K., Debnam, E. and Rice-Evans, C. (2000) Decomposition of cocoa procyanidins in the gastric milieu. Biochem. Biophys. Res. Commun., 272, 236-241. https://doi.org/10.1006/bbrc.2000.2749
  90. Cooper, K.A., Donovan, J.L., Waterhouse, A.L. and Williamson, G. (2008) Cocoa and health: a decade of research. Br. J. Nutr., 99, 1-11.
  91. Schroeter, H. (2004) Flavonoids, neuroprotective agent? Modulation of oxidative stress-induced MAP kinase signaling transduction in Flavonoids in Health and Disease (Packer, L. and Rice-Evans, C.A. Eds.). Marcel Dekker, New York, pp. 233-272.
  92. Spencer, J.P., Abd-el-Mohsen, M.M. and Rice-Evans, C. (2004) Cellular uptake and metabolism of flavonoids and their metabolites: implications for their bioactivity. Arch. Biochem. Biophys., 423, 148-161. https://doi.org/10.1016/j.abb.2003.11.010
  93. Stoupi, S., Williamson, G., Viton, F., Barron, D., King, L.J., Brown, J.E. and Clifford, M.N. (2010) In vivo bioavailability, absorption, excretion, and pharmacokinetics of [14C]procyanidin B2 in male rats. Drug Metab. Dispos., 38, 287-291. https://doi.org/10.1124/dmd.109.030304
  94. Zhang, L., Wang, Y., Li, D., Ho, C.T., Li, J. and Wan, X. (2016) The absorption, distribution, metabolism and excretion of procyanidins. Food Funct., 7, 1273-1281. https://doi.org/10.1039/C5FO01244A
  95. Holt, R.R., Lazarus, S.A., Sullards, M.C., Zhu, Q.Y., Schramm, D.D. Hammerstone, J.F., Fraga, C.G., Schmitz, H.H. and Keen, C.L. (2002) Procyanidin dimer $B_2$ [epicatechin-(4beta-8)-epicatechin] in human plasma after the consumption of a flavanol-rich cocoa. Am. J. Clin. Nutr., 76, 798-804. https://doi.org/10.1093/ajcn/76.4.798
  96. Vigna, G.B., Costantini, F., Aldini, G., Carini, M., Catapano, A., Schena, F., Tangerini, A., Zanca, R., Bombardelli, E., Morazzoni, P., Mezzetti, A., Fellin, R. and Maffei Facino, R. (2003) Effect of a standardized grape seed extract on low-density lipoprotein susceptibility to oxidation in heavy smokers. Metabolism, 52, 1250-1257. https://doi.org/10.1016/S0026-0495(03)00192-6

Cited by

  1. L.) pp.01458884, 2018, https://doi.org/10.1111/jfbc.12680
  2. Inhibition of di(2-ethylhexyl) phthalate (DEHP)-induced endocrine disruption by co-treatment of vitamins C and E and their mechanism of action vol.81, pp.16, 2018, https://doi.org/10.1080/15287394.2018.1473262