Evaluation of Xanthohumol as a potent drug from nature: Synthesis, isolation and anticancer activity

Volume 4, Issue 1, February 2019     |     PP. 1-19      |     PDF (809 K)    |     Pub. Date: March 20, 2019
DOI:    422 Downloads     7052 Views  

Author(s)

Kyriaki S. Pafiti, University of Nicosia, Department of Life Sciences, P.O. Box 24005, 1700, Nicosia, Cyprus.
Manolis Ch. Vlasiou, University of Cyprus, Department of Chemistry, P.O. Box 20537, 1678 Nicosia, Cyprus.

Abstract
In this paper we are reviewing the potent anticancer activity of xanthohumol (XN) molecule and its analogues. The anticancer activity is explained according to the mechanisms of action of the molecule on tumour cells. We also comparing the isolation techniques and the synthetic routes that have been developed as far as now, indicating the most reasonable way of taking this molecule for preliminary studies. Finally, we are giving our opinion of future research that it is preferable to been followed based on these findings.

Keywords
xantohumol, synthesis, isolation, anticancer

Cite this paper
Kyriaki S. Pafiti, Manolis Ch. Vlasiou, Evaluation of Xanthohumol as a potent drug from nature: Synthesis, isolation and anticancer activity , SCIREA Journal of Chemistry. Volume 4, Issue 1, February 2019 | PP. 1-19.

References

[ 1 ] Acharya, D. P., Sanguansri, L. and Augustin, M. A. (2013) ‘Binding of resveratrol with sodium caseinate in aqueous solutions’, Food Chemistry. Elsevier Ltd, 141(2), pp. 1050–1054. doi: 10.1016/j.foodchem.2013.03.037.
[ 2 ] Anioł, M., Szymańska, K. and Zołnierczyk, A. (2008) ‘An efficient synthesis of the phytoestrogen 8-prenylnaringenin from isoxanthohumol with magnesium iodide etherate’, Tetrahedron, 64(40), pp. 9544–9547. doi: 10.1016/j.tet.2008.07.072.
[ 3 ] Cai, X. P. et al. (2014) ‘Tunable photoluminescence properties of [Ru(bpy)2(tatp)]2+bound to a BSA-SWCNTs film upon incorporation of [Co(phen)3]3+’, Journal of Photochemistry and Photobiology A: Chemistry. Elsevier B.V., 291, pp. 1–8. doi: 10.1016/j.jphotochem.2014.06.016.
[ 4 ] Cassidy, C. E. and Setzer, W. N. (2010) ‘Cancer-relevant biochemical targets of cytotoxic Lonchocarpus flavonoids: A molecular docking analysis’, Journal of Molecular Modeling, 16(2), pp. 311–326. doi: 10.1007/s00894-009-0547-5.
[ 5 ] Castan, S. et al. (2005) ‘A fast, sensitive method for the simultaneous determination of alpha-tocopherol and alpha-tocopheryl acetate in mixed micelles.’, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, 822(1–2), pp. 339–346. doi: 10.1016/j.jchromb.2005.06.028.
[ 6 ] Cetin-Karaca, H. and Newman, M. C. (2015) ‘Antimicrobial efficacy of plant phenolic compounds against Salmonella and Escherichia Coli’, Food Bioscience. Elsevier, 11, pp. 8–15. doi: 10.1016/j.fbio.2015.03.002.
[ 7 ] Chadwick, L. R. et al. (2005) ‘CCC Sample Cutting for Isolation of Prenylated Phenolics from Hops’, Journal of Liquid Chromatography & Related Technologies, 28(28), pp. 37–41. doi: 10.1081/Jlc-200063634.
[ 8 ] Chen, Q. et al. (2012) ‘Preparative isolation and purification of xanthohumol from hops (Humulus lupulus L.) by high-speed counter-current chromatography’, Food Chemistry. Elsevier Ltd, 132(1), pp. 619–623. doi: 10.1016/j.foodchem.2011.10.098.
[ 9 ] Diller, R. a. et al. (2005) ‘Synthesis of demethylxanthohumol, a new potent apoptosis-inducing agent from hops’, Chemistry and Biodiversity, 2(10), pp. 1331–1337. doi: 10.1002/cbdv.200590105.
[ 10 ] Ellinwood, D. C. et al. (2017) ‘Total synthesis of [13C]2-, [13C]3-, and [13C]5-isotopomers of xanthohumol, the principal prenylflavonoid from hops’, Journal of Labelled Compounds and Radiopharmaceuticals, 60(14), pp. 639–648. doi: 10.1002/jlcr.3571.
[ 11 ] Ferk, F. et al. (2010) ‘Xanthohumol, a prenylated flavonoid contained in beer, prevents the induction of preneoplastic lesions and DNA damage in liver and colon induced by the heterocyclic aromatic amine amino-3-methyl-imidazo[4,5-f]quinoline (IQ)’, Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 691(1–2), pp. 17–22. doi: 10.1016/j.mrfmmm.2010.06.006.
[ 12 ] Ferk, F. et al. (2016) ‘Impact of xanthohumol (a prenylated flavonoid from hops) on DNA stability and other health-related biochemical parameters: Results of human intervention trials’, Molecular Nutrition and Food Research, 60(4), pp. 773–786. doi: 10.1002/mnfr.201500355.
[ 13 ] Gerhauser, C. et al. (2002) ‘Cancer Chemopreventive Activity of Xanthohumol , a Natural Product Derived from Hop 1 Support for this work has been provided by Verein zur Förderung der Krebsforschung in Deutschland e . V . and by Wissenschaftsförderung der Deutschen Brauwirtschaft e . ’.
[ 14 ] Gerhäuser, C. (2005a) ‘Beer constituents as potential cancer chemopreventive agents’, European Journal of Cancer, 41(13), pp. 1941–1954. doi: 10.1016/j.ejca.2005.04.012.
[ 15 ] Gerhäuser, C. (2005b) ‘Broad spectrum antiinfective potential of xanthohumol from hop (Humulus lupulus L.) in comparison with activities of other hop constituents and xanthohumol metabolites’, Molecular Nutrition and Food Research, 49(9), pp. 827–831. doi: 10.1002/mnfr.200500091.
[ 16 ] Gil-Ramírez, A. et al. (2012) ‘Highly isoxanthohumol enriched hop extract obtained by pressurized hot water extraction (PHWE). Chemical and functional characterization’, Innovative Food Science and Emerging Technologies. Elsevier Ltd, 16, pp. 54–60. doi: 10.1016/j.ifset.2012.04.006.
[ 17 ] Gliszczyńska-świgło, A. et al. (2007) ‘Tocopherol content in edible plant oils’, Polish Journal of Food and Nutrition Sciences, 57(4), pp. 157–161.
[ 18 ] Guo, D. et al. (2018) ‘Xanthohumol induces apoptosis via caspase activation, regulation of Bcl-2, and inhibition of PI3K/Akt/mTOR-kinase in human gastric cancer cells’, Biomedicine and Pharmacotherapy. Elsevier, 106(June), pp. 1300–1306. doi: 10.1016/j.biopha.2018.06.166.
[ 19 ] Jacob, C., Jamier, V. and Ba, L. A. (2011) ‘Redox active secondary metabolites’, Current Opinion in Chemical Biology. Elsevier Ltd, 15(1), pp. 149–155. doi: 10.1016/j.cbpa.2010.10.015.
[ 20 ] Jiang, C. H. et al. (2018) ‘Anticancer activity and mechanism of xanthohumol: A prenylated flavonoid from hops (Humulus lupulus L.)’, Frontiers in Pharmacology, 9(MAY), pp. 1–13. doi: 10.3389/fphar.2018.00530.
[ 21 ] Jiang, W. et al. (2015) ‘The inhibitory effects of xanthohumol, a prenylated chalcone derived from hops, on cell growth and tumorigenesis in human pancreatic cancer’, Biomedicine and Pharmacotherapy. Elsevier Masson SAS, 73, pp. 40–47. doi: 10.1016/j.biopha.2015.05.020.
[ 22 ] Kac, J. et al. (2008) ‘Antimutagenicity of hops (Humulus lupulus L.): bioassay-directed fractionation and isolation of xanthohumol’, Phytomedicine, 15(3), pp. 216–220. doi: 10.1016/j.phymed.2007.09.008.
[ 23 ] Kakati, D. and Sarma, J. C. (2011) ‘Microwave assisted solvent free synthesis of 1,3-diphenylpropenones.’, Chemistry Central journal. Chemistry Central Ltd, 5(1), p. 8. doi: 10.1186/1752-153X-5-8.
[ 24 ] Karimi-Sales, E., Mohaddes, G. and Alipour, M. R. (2018) ‘Chalcones as putative hepatoprotective agents: Preclinical evidence and molecular mechanisms’, Pharmacological Research. Elsevier Ltd, 129, pp. 177–187. doi: 10.1016/j.phrs.2017.11.022.
[ 25 ] Keiler, A. M., Zierau, O. and Kretzschmar, G. (2013) ‘Hop extracts and hop substances in treatment of menopausal complaints’, Planta Medica, 79(7), pp. 576–579. doi: 10.1055/s-0032-1328330.
[ 26 ] Kunnimalaiyaan, S. et al. (2015) ‘Xanthohumol-Mediated Suppression of Notch1 Signaling Is Associated with Antitumor Activity in Human Pancreatic Cancer Cells’, Molecular Cancer Therapeutics, 14(6), pp. 1395–1403. doi: 10.1158/1535-7163.MCT-14-0915.
[ 27 ] Leonida, M. D. et al. (2018) ‘Antibacterial hop extracts encapsulated in nanochitosan matrices’, International Journal of Biological Macromolecules. Elsevier B.V., 120, pp. 1335–1343. doi: 10.1016/j.ijbiomac.2018.09.003.
[ 28 ] Li, F. et al. (2018) ‘Xanthohumol attenuates cisplatin-induced nephrotoxicity through inhibiting NF-κB and activating Nrf2 signaling pathways’, International Immunopharmacology. Elsevier, 61(June), pp. 277–282. doi: 10.1016/j.intimp.2018.05.017.
[ 29 ] Magalhães, P. J. et al. (2010) ‘Isolation of phenolic compounds from hop extracts using polyvinylpolypyrrolidone: Characterization by high-performance liquid chromatography-diode array detection-electrospray tandem mass spectrometry’, Journal of Chromatography A, 1217(19), pp. 3258–3268. doi: 10.1016/j.chroma.2009.10.068.
[ 30 ] Mi, X. et al. (2017) ‘Xanthohumol induces paraptosis of leukemia cells through p38 mitogen activated protein kinase signaling pathway.’, Oncotarget, 8(19), pp. 31297–31304. doi: 10.18632/oncotarget.16185.
[ 31 ] Miyata, S. et al. (2015) ‘Xanthohumol improves diet-induced obesity and fatty liver by suppressing Sterol Regulatory Element-binding Protein (SREBP) activation’, Journal of Biological Chemistry, 290(33), pp. 20565–20579. doi: 10.1074/jbc.M115.656975.
[ 32 ] Nava, P. et al. (2006) ‘Preparation of fluorescent tocopherols for use in protein binding and localization with the ??-tocopherol transfer protein’, Bioorganic and Medicinal Chemistry, 14(11), pp. 3721–3736. doi: 10.1016/j.bmc.2006.01.053.
[ 33 ] Nozawa, H. (2005) ‘Xanthohumol, the chalcone from beer hops (Humulus lupulus L.), is the ligand for farnesoid X receptor and ameliorates lipid and glucose metabolism in KK-Ay mice’, Biochemical and Biophysical Research Communications, 336(3), pp. 754–761. doi: 10.1016/j.bbrc.2005.08.159.
[ 34 ] Nuti, E. et al. (2017) ‘Synthesis and antiangiogenic activity study of new hop chalcone Xanthohumol analogues’, European Journal of Medicinal Chemistry. Elsevier Masson SAS, 138, pp. 890–899. doi: 10.1016/j.ejmech.2017.07.024.
[ 35 ] Passalacqua, T. G. et al. (2015) ‘Synthesis and evaluation of novel prenylated chalcone derivatives as anti-leishmanial and anti-trypanosomal compounds’, Bioorganic and Medicinal Chemistry Letters. Elsevier Ltd, 25(16), pp. 3342–3345. doi: 10.1016/j.bmcl.2015.05.072.
[ 36 ] Popło´ nski, J. et al. (2018) ‘Synthesis and antiproliferative activity of minor hops prenylflavonoids and new insights on prenyl group cyclization’, Molecules, 23(4). doi: 10.3390/molecules23040776.
[ 37 ] Radović, B., Schmutzler, C. and Köhrle, J. (2005) ‘Xanthohumol stimulates iodide uptake in rat thyroid-derived FRTL-5 cells’, Molecular Nutrition and Food Research, 49(9), pp. 832–836. doi: 10.1002/mnfr.200500053.
[ 38 ] Seliger, J. M. et al. (2018) ‘The hop-derived compounds xanthohumol, isoxanthohumol and 8-prenylnaringenin are tight-binding inhibitors of human aldo-keto reductases 1B1 and 1B10’, Journal of Enzyme Inhibition and Medicinal Chemistry. Informa UK Ltd., 33(1), pp. 607–614. doi: 10.1080/14756366.2018.1437728.
[ 39 ] Sławińska-Brych, A. et al. (2015) ‘Xanthohumol inhibits cell cycle progression and proliferation of larynx cancer cells in vitro’, Chemico-Biological Interactions, 240, pp. 110–118. doi: 10.1016/j.cbi.2015.08.008.
[ 40 ] Sławińska-Brych, A. et al. (2016) ‘Xanthohumol inhibits the extracellular signal regulated kinase (ERK) signalling pathway and suppresses cell growth of lung adenocarcinoma cells’, Toxicology, 357–358, pp. 65–73. doi: 10.1016/j.tox.2016.06.008.
[ 41 ] Stevens, J. F. and Page, J. E. (2004) ‘Xanthohumol and related prenylflavonoids from hops and beer: To your good health!’, Phytochemistry, 65(10), pp. 1317–1330. doi: 10.1016/j.phytochem.2004.04.025.
[ 42 ] Strathmann, J. et al. (2010) ‘Xanthohumol-induced transient superoxide anion radical formation triggers cancer cells into apoptosis via a mitochondria-mediated mechanism.’, The FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 24(8), pp. 2938–2950. doi: 10.1096/fj.10-155846.
[ 43 ] Suh, K. S. et al. (2018) ‘Xanthohumol ameliorates 2,3,7,8-tetrachlorodibenzo-p-dioxin–induced cellular toxicity in cultured MC3T3-E1 osteoblastic cells’, Journal of Applied Toxicology, 38(7), pp. 1036–1046. doi: 10.1002/jat.3613.
[ 44 ] Sun, Z. et al. (2017) ‘Inhibition of breast cancer cell survival by Xanthohumol via modulation of the Notch signaling pathway in�vivo and in�vitro’, Oncology Letters, pp. 908–916. doi: 10.3892/ol.2017.7434.
[ 45 ] Sung, B. et al. (2012) ‘Cancer Cell Signaling Pathways Targeted by Spice-Derived Nutraceuticals’, Nutrition and Cancer, 64(2), pp. 173–197. doi: 10.1080/01635581.2012.630551.
[ 46 ] Venturelli, S. et al. (2016) ‘Prenylated chalcones and flavonoids for the prevention and treatment of cancer’, Nutrition. Elsevier Inc., 32(11–12), pp. 1171–1178. doi: 10.1016/j.nut.2016.03.020.
[ 47 ] Vogel, S. et al. (2008) ‘Natural and non-natural prenylated chalcones: Synthesis, cytotoxicity and anti-oxidative activity’, Bioorganic and Medicinal Chemistry, 16(8), pp. 4286–4293. doi: 10.1016/j.bmc.2008.02.079.
[ 48 ] Vogel, S. et al. (2010) ‘Synthesis, cytotoxicity, anti-oxidative and anti-inflammatory activity of chalcones and influence of A-ring modifications on the pharmacological effect’, European Journal of Medicinal Chemistry, 45(6), pp. 2206–2213. doi: 10.1016/j.ejmech.2010.01.060.
[ 49 ] Yong, R. L. et al. (2008) ‘Concise total synthesis of biologically interesting prenylated chalcone natural products: 4′-O-methylxanthohumol, xanthohumol E, and sericone’, Bulletin of the Korean Chemical Society, 29(6), pp. 1205–1210. doi: 10.5012/bkcs.2008.29.6.1205.
[ 50 ] Yong, W. K., Nurestri, S. and Malek, A. (2015) ‘XAnthohumol’, 2015.
[ 51 ] Zhang, B. et al. (2015) ‘Synthesis of xanthohumol analogues and discovery of potent thioredoxin reductase inhibitor as potential anticancer agent’, Journal of Medicinal Chemistry, 58(4), pp. 1795–1805. doi: 10.1021/jm5016507.
[ 52 ] Zhang, C. X. and Lippard, S. J. (2003) ‘New metal complexes as potential therapeutics’, Current Opinion in Chemical Biology, 7(4), pp. 481–489. doi: 10.1016/S1367-5931(03)00081-4.
[ 53 ] Zhao, X. et al. (2016) ‘Anticancer effect of xanthohumol induces growth inhibition and apoptosis of human liver cancer through NF-B/p53-apoptosis signaling pathway’, Oncology Reports, 35(2), pp. 669–675. doi: 10.3892/or.2015.4455.
[ 54 ] Zołnierczyk, A. K. et al. (2015) ‘Isoxanthohumol - Biologically active hop flavonoid’, Fitoterapia, 103, pp. 71–82. doi: 10.1016/j.fitote.2015.03.007.