Login Register Cart 0
Generic placeholder image

Current Bioactive Compounds

Editor-in-Chief

ISSN (Print): 1573-4072
ISSN (Online): 1875-6646

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Mini-Review Article

Natural Compounds for Carcinoma Therapy by Wingless Signaling Pathway Down-regulation

Author(s): Smriti Ojha, Rahul Kumar Mishra, Sudhanshu Mishra*, Amrita Singh and Shweta Kumari

Volume 19, Issue 6, 2023

Published on: 10 March, 2023

Article ID: e020223213388 Pages: 5

DOI: 10.2174/1573407219666230202141915

Price: $65

Abstract

Cancer is a prominent cause of death that places a significant financial strain on the healthcare system. Because of its prevalence, there is unquestionably unmet need for new chemotherapeutics. Atypical activation and deregulation of the wingless (Wnt) signaling pathway are considered one of the major causes of various types of carcinomas. This receptor activation is directly correlated with the activation of β -catenin and β -catenin-dependent transcription. In the modern era of drug development, natural compounds have shown to be an unrivaled source of anticancer medications. Herbal compounds have been identified as potent β-catenin signaling inhibitors, mainly by their downregulation, modulating its phosphorylation, increasing ubiquitination and proteasomal destruction, blocking nuclear translocation, or other molecular mechanisms. In vitro and in vivo studies have revealed that these natural product inhibitors can prevent and treat cancer in a variety of cancer models. Natural products have the potential to be promising novel molecules for cancer treatment, making them an essential topic of study. The importance of natural products in blocking the numerous signaling pathways that promote carcinogenesis is explored in this review, paving the way for developing and discovering anticancer medicines.

Graphical Abstract

[1]
Luo, J.; Chen, J.; Deng, Z.L.; Luo, X.; Song, W.X.; Sharff, K.A.; Tang, N.; Haydon, R.C.; Luu, H.H.; He, T.C. Wnt signaling and human diseases: what are the therapeutic implications? Lab. Invest., 2007, 87(2), 97-103.
[http://dx.doi.org/10.1038/labinvest.3700509] [PMID: 17211410]
[2]
Wodarz, A.; Nusse, R. Mechanisms of Wnt signaling in development. Annu. Rev. Cell Dev. Biol., 1998, 14(1), 59-88.
[http://dx.doi.org/10.1146/annurev.cellbio.14.1.59] [PMID: 9891778]
[3]
Zhang, B.; Ma, J. Wnt pathway antagonists and angiogenesis. Protein Cell, 2010, 1(10), 898-906.
[http://dx.doi.org/10.1007/s13238-010-0112-0] [PMID: 21204016]
[4]
Schulte, G. Frizzleds and WNT/β-catenin signaling - The black box of ligand–receptor selectivity, complex stoichiometry and activation kinetics. Eur. J. Pharmacol.,, 2015, 763(Pt B), 191-195.
[http://dx.doi.org/10.1016/j.ejphar.2015.05.031] [PMID: 26003275]
[5]
Sharma, D.; Mishra, S.; Rajput, A.; Raj, K.; Malviya, R. Pathophysiology and biomarkers for breast cancer: Management using herbal medicines. Curr. Nutr. Food Sci., 2021, 17(9), 974-984.
[http://dx.doi.org/10.2174/1573401317666210713114216]
[6]
Roy, L.; Cowden Dahl, K. Can stemness and chemoresistance be therapeutically targeted via signaling pathways in ovarian cancer? Cancers (Basel), 2018, 10(8), 241.
[http://dx.doi.org/10.3390/cancers10080241] [PMID: 30042330]
[7]
MacDonald, B.T.; He, X. Frizzled and LRP5/6 receptors for Wnt/β-catenin signaling. Cold Spring Harb. Perspect. Biol., 2012, 4(12), a007880.
[http://dx.doi.org/10.1101/cshperspect.a007880] [PMID: 23209147]
[8]
Shaw, H.V.; Koval, A.; Katanaev, V.L. Targeting the Wnt signalling pathway in cancer: prospects and perils. Swiss Med. Wkly., 2019, 149, w20129.
[http://dx.doi.org/10.4414/smw.2019.20129] [PMID: 31579927]
[9]
De, A. Wnt/Ca<sup>2+</sup> signaling pathway: a brief overview. Acta Biochim. Biophys. Sin. (Shanghai), 2011, 43(10), 745-756.
[http://dx.doi.org/10.1093/abbs/gmr079] [PMID: 21903638]
[10]
Krausova, M.; Korinek, V. Wnt signaling in adult intestinal stem cells and cancer. Cell. Signal., 2014, 26(3), 570-579.
[http://dx.doi.org/10.1016/j.cellsig.2013.11.032] [PMID: 24308963]
[11]
Nusse, R.; Varmus, H.E. Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome. Cell, 1982, 31(1), 99-109.
[http://dx.doi.org/10.1016/0092-8674(82)90409-3] [PMID: 6297757]
[12]
Whyte, J.L.; Smith, A.A.; Helms, J.A. Wnt signaling and injury repair. Cold Spring Harb. Perspect. Biol., 2012, 4(8), a008078.
[http://dx.doi.org/10.1101/cshperspect.a008078] [PMID: 22723493]
[13]
Polakis, P. Drugging Wnt signalling in cancer. EMBO J., 2012, 31(12), 2737-2746.
[http://dx.doi.org/10.1038/emboj.2012.126] [PMID: 22617421]
[14]
Ahmed, K.; Shaw, H.; Koval, A.; Katanaev, V. A second WNT for old drugs: drug repositioning against WNT-dependent cancers. Cancers (Basel), 2016, 8(7), 66.
[http://dx.doi.org/10.3390/cancers8070066] [PMID: 27429001]
[15]
Koval, A.; Katanaev, V.L. Wnt3a stimulation elicits G-protein-coupled receptor properties of mammalian Frizzled proteins. Biochem. J., 2011, 433(3), 435-440.
[http://dx.doi.org/10.1042/BJ20101878] [PMID: 21128903]
[16]
Neiheisel, A.; Kaur, M.; Ma, N.; Havard, P.; Shenoy, A.K. Wnt pathway modulators in cancer therapeutics: An update on completed and ongoing clinical trials. Int. J. Cancer, 2022, 150(5), 727-740.
[http://dx.doi.org/10.1002/ijc.33811] [PMID: 34536299]
[17]
Park, C.H.; Chang, J.Y.; Hahm, E.R.; Park, S.; Kim, H.K.; Yang, C.H. Quercetin, a potent inhibitor against β-catenin/Tcf signaling in SW480 colon cancer cells. Biochem. Biophys. Res. Commun., 2005, 328(1), 227-234.
[http://dx.doi.org/10.1016/j.bbrc.2004.12.151] [PMID: 15670774]
[18]
Swami, S.; Krishnan, A.V.; Wang, J.Y.; Jensen, K.; Horst, R.; Albertelli, M.A.; Feldman, D. Dietary vitamin D3 and 1,25-dihydroxyvitamin D3 (calcitriol) exhibit equivalent anticancer activity in mouse xenograft models of breast and prostate cancer. Endocrinology, 2012, 153(6), 2576-2587.
[http://dx.doi.org/10.1210/en.2011-1600] [PMID: 22454149]
[19]
Kim, J.; Zhang, X.; Rieger-Christ, K.M.; Summerhayes, I.C.; Wazer, D.E.; Paulson, K.E.; Yee, A.S. Suppression of Wnt signaling by the green tea compound (-)-epigallocatechin 3-gallate (EGCG) in invasive breast cancer cells. Requirement of the transcriptional repressor HBP1. J. Biol. Chem., 2006, 281(16), 10865-10875.
[http://dx.doi.org/10.1074/jbc.M513378200] [PMID: 16495219]
[20]
Hansen, L.A.; Sigman, C.C.; Andreola, F.; Ross, S.A.; Kelloff, G.J.; De Luca, L.M. Retinoids in chemoprevention and differentiation therapy. Carcinogenesis, 2000, 21(7), 1271-1279.
[http://dx.doi.org/10.1093/carcin/21.7.1271] [PMID: 10874003]
[21]
Rao, C.V.; Desai, D.; Rivenson, A.; Simi, B.; Amin, S.; Reddy, B.S. Chemoprevention of colon carcinogenesis by phenylethyl-3-methylcaffeate. Cancer Res., 1995, 55(11), 2310-2315.
[PMID: 7757981]
[22]
Jaiswal, A.S.; Marlow, B.P.; Gupta, N.; Narayan, S. β-Catenin-mediated transactivation and cell–cell adhesion pathways are important in curcumin (diferuylmethane)-induced growth arrest and apoptosis in colon cancer cells. Oncogene, 2002, 21(55), 8414-8427.
[http://dx.doi.org/10.1038/sj.onc.1205947] [PMID: 12466962]
[23]
Roccaro, A.M.; Leleu, X.; Sacco, A.; Moreau, A.S.; Hatjiharissi, E.; Jia, X.; Xu, L.; Ciccarelli, B.; Patterson, C.J.; Ngo, H.T.; Russo, D.; Vacca, A.; Dammacco, F.; Anderson, K.C.; Ghobrial, I.M.; Treon, S.P. Resveratrol exerts antiproliferative activity and induces apoptosis in Waldenström’s macroglobulinemia. Clin. Cancer Res., 2008, 14(6), 1849-1858.
[http://dx.doi.org/10.1158/1078-0432.CCR-07-1750] [PMID: 18347188]
[24]
Morris, H.R.; Taylor, G.W.; Masento, M.S.; Jermyn, K.A.; Kay, R.R. Chemical structure of the morphogen differentiation inducing factor from Dictyostelium discoideum. Nature, 1987, 328(6133), 811-814.
[http://dx.doi.org/10.1038/328811a0] [PMID: 3627228]
[25]
Ryu, M.J.; Cho, M.; Song, J.Y.; Yun, Y.S.; Choi, I.W.; Kim, D.E.; Park, B.S.; Oh, S. Natural derivatives of curcumin attenuate the Wnt/β-catenin pathway through down-regulation of the transcriptional coactivator p300. Biochem. Biophys. Res. Commun., 2008, 377(4), 1304-1308.
[http://dx.doi.org/10.1016/j.bbrc.2008.10.171] [PMID: 19000900]
[26]
Park, C.H.; Hahm, E.R.; Park, S.; Kim, H.K.; Yang, C.H. The inhibitory mechanism of curcumin and its derivative against β-catenin/Tcf signaling. FEBS Lett., 2005, 579(13), 2965-2971.
[http://dx.doi.org/10.1016/j.febslet.2005.04.013] [PMID: 15893313]
[27]
Srivastava, N.S.; Srivastava, R.A.K. Curcumin and quercetin synergistically inhibit cancer cell proliferation in multiple cancer cells and modulate Wnt/β-catenin signaling and apoptotic pathways in A375 cells. Phytomedicine, 2019, 52, 117-128.
[http://dx.doi.org/10.1016/j.phymed.2018.09.224] [PMID: 30599890]
[28]
Yang, C.; Du, W.; Yang, D. Inhibition of green tea polyphenol EGCG((−)-epigallocatechin-3-gallate) on the proliferation of gastric cancer cells by suppressing canonical wnt/β-catenin signalling pathway. Int. J. Food Sci. Nutr., 2016, 67(7), 818-827.
[http://dx.doi.org/10.1080/09637486.2016.1198892] [PMID: 27338284]
[29]
Frémont, L. Biological effects of resveratrol. Life Sci., 2000, 66(8), 663-673.
[http://dx.doi.org/10.1016/S0024-3205(99)00410-5] [PMID: 10680575]
[30]
Sheremet, M.; Kapoor, S.; Schröder, P.; Kumar, K.; Ziegler, S.; Waldmann, H. Small molecules inspired by the natural product withanolides as potent inhibitors of Wnt signaling. ChemBioChem, 2017, 18(18), 1797-1806.
[http://dx.doi.org/10.1002/cbic.201700260] [PMID: 28678390]
[31]
Palermo, R.; Ghirga, F.; Piccioni, M.G.; Bernardi, F.; Zhdanovskaya, N.; Infante, P.; Mori, M. Natural products inspired modulators of cancer stem cells-specific signaling pathways Notch and Hedgehog. Curr. Pharm. Des., 2019, 24(36), 4251-4269.
[http://dx.doi.org/10.2174/1381612825666190111124822] [PMID: 30636589]
[32]
Fatima, I.; El-Ayachi, I.; Taotao, L.; Lillo, M.A.; Krutilina, R.; Seagroves, T.N.; Radaszkiewicz, T.W.; Hutnan, M.; Bryja, V.; Krum, S.A.; Rivas, F.; Miranda-Carboni, G.A. The natural compound Jatrophone interferes with Wnt/β-catenin signaling and inhibits proliferation and EMT in human triple-negative breast cancer. PLoS One, 2017, 12(12), e0189864.
[http://dx.doi.org/10.1371/journal.pone.0189864] [PMID: 29281678]
[33]
Ling, T.; Hadi, V.; Guiguemde, A.; Landfear, S.M.; Rivas, F. Jatropha natural products as potential therapeutic leads. In: The Formation, Structure, and Activity of Phytochemicals; Springer: Cham, 2015; pp. 77-98.
[http://dx.doi.org/10.1007/978-3-319-20397-3_3]
[34]
Patel, S.; Alam, A.; Pant, R.; Chattopadhyay, S. Wnt signaling and its significance within the tumor microenvironment: novel therapeutic insights. Front. Immunol., 2019, 10, 2872.
[http://dx.doi.org/10.3389/fimmu.2019.02872] [PMID: 31921137]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy