Login Register Cart 0
Generic placeholder image

Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Acteoside (Verbascoside): A Prospective Therapeutic Alternative against Hepatocellular Carcinoma by Inhibiting the Expression of AXL, FGFR, BRAF, TIE2 and RAF1 Targets

Author(s): Sibashish Kityania, Rajat Nath, Deepa Nath, Jayanta Kumar Patra and Anupam Das Talukdar*

Volume 26, Issue 10, 2023

Published on: 27 December, 2022

Page: [1907 - 1919] Pages: 13

DOI: 10.2174/1386207326666221031121426

Price: $65

Abstract

Aim: Hepatocellular carcinoma (HCC) is the world's second leading cause of cancerrelated mortality and the fifth most prevalent cancer overall. Several synthetic and plant-based remedies are in practice to treat diverse liver disorders. Because of their minimal side effects and protective characteristics, plant phenolics have the potential to become alternative therapeutics, replacing currently existing HCC medications. The present study identifies the plant phenolics as having the capacity to inhibit HCC with low side effects and cost efficiency.

Background: Hepatocellular carcinoma (HCC) is the leading cause of cancer-related mortality, despite the proven effectiveness of screening programs for at-risk individuals, the majority of patients have disease progression or tumor characteristics that preclude curative therapies at the time of diagnosis. Acteoside (Verbascoside) is a naturally occurring phenylethanoid glycoside found throughout the plant kingdom. Acteoside is a physiologically active chemical with the number of pharmacological and protective effects against various liver illnesses.

Objectives: Currently used HCC medications have a variety of side effects. Plant-based chemicals offer the possibility of treating HCC with minimal side effects. The work is targeted to find the best phytochemical (plant phenolic) lead molecule for future drug development research against Hepatocellular carcinoma.

Methods: The targets were selected based on an analysis of relevant literature, and the 3D structures of the selected receptors were obtained in. pdb format from the RCSB-Protein data bank (PDB, http://www.rscb.org/pdb). Based on a review of the literature, sixty plant secondary metabolites, or plant phenolics, were selected. The ligand structures were obtained and downloaded in.sdf format from the NCBI PubChem chemicals database (https://pubchem.ncbi.nlm.nih.gov/). Molecular docking between the receptor and ligands was accomplished using the Molegro Virtual Docker 6.0 (MVD) software.

Results: The target RAF1, BRAF chain 1, TIE2 chain 2 FGFR1, FGFR2, AXL, and FGFR4 showed the best binding effectiveness with acteoside compared to their respective positive control. RET chain 1 and BRAF chain 2 acteoside showed prominent binding efficacy after Curcumin, and Epigallocatechingallate, respectively, against positive control. Present findings clearly point towards the potentiality of acteoside in inhibiting various HCC targets.

Conclusion: Acteoside may be used as a prominent lead molecule in the future treatment of hepatic cancer with its multifaceted binding efficiencies against various target proteins.

Keywords: Natural phenolics, acteoside, hepatocellular carcinoma (HCC), molecular docking, drug lead, cancer-related mortality.

« Previous Next »
Graphical Abstract

[1]
Ma, Y.S.; Lv, Z.W.; Yu, F.; Chang, Z.Y.; Cong, X.L.; Zhong, X.M.; Lu, G.X.; Zhu, J.; Fu, D. MicroRNA-302a/d inhibits the self-renewal capability and cell cycle entry of liver cancer stem cells by targeting the E2F7/AKT axis. J. Exp. Clin. Cancer Res., 2018, 37(1), 252.
[http://dx.doi.org/10.1186/s13046-018-0927-8] [PMID: 30326936]
[2]
Ma, Y.S.; Liu, J.B.; Wu, T.M.; Fu, D. New therapeutic options for advanced hepatocellular carcinoma. Cancer Contr., 2020, 27(3), 1073274820945975.
[http://dx.doi.org/10.1177/1073274820945975] [PMID: 32799550]
[3]
Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2018, 68(6), 394-424.
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
[4]
Sun, J.; Luo, Q.; Liu, L.; Song, G. Low-level shear stress promotes migration of liver cancer stem cells via the FAK-ERK1/2 signalling pathway. Cancer Lett., 2018, 427, 1-8.
[http://dx.doi.org/10.1016/j.canlet.2018.04.015] [PMID: 29678550]
[5]
Abou-El-Enein, M.; Grainger, D.W.; Kili, S. Registry contributions to strengthen cell and gene therapeutic evidence. Mol. Ther., 2018, 26(5), 1172-1176.
[http://dx.doi.org/10.1016/j.ymthe.2018.04.007] [PMID: 29685384]
[6]
Monsuez, J.J.; Charniot, J.C.; Vignat, N.; Artigou, J.Y. Cardiac side-effects of cancer chemotherapy. Int. J. Cardiol., 2010, 144(1), 3-15.
[http://dx.doi.org/10.1016/j.ijcard.2010.03.003] [PMID: 20399520]
[7]
Raoul, J.L.; Kudo, M.; Finn, R.S.; Edeline, J.; Reig, M.; Galle, P.R. Systemic therapy for intermediate and advanced hepatocellular carcinoma: Sorafenib and beyond. Cancer Treat. Rev., 2018, 68, 16-24.
[http://dx.doi.org/10.1016/j.ctrv.2018.05.006] [PMID: 29783126]
[8]
Lee, J.K.; Abou-Alfa, G.K. An update on clinical trials in the treatment of advanced hepatocellular carcinoma. J. Clin. Gastroenterol., 2013, 47(Suppl. 1), S16-S19.
[http://dx.doi.org/10.1097/MCG.0b013e31827d77a2] [PMID: 23751800]
[9]
Bruix, J.; Tak, W.Y.; Gasbarrini, A.; Santoro, A.; Colombo, M.; Lim, H.Y.; Mazzaferro, V.; Wiest, R.; Reig, M.; Wagner, A.; Bolondi, L. Regorafenib as second-line therapy for intermediate or advanced hepatocellular carcinoma: Multicentre, open-label, phase II safety study. Eur. J. Cancer, 2013, 49(16), 3412-3419.
[http://dx.doi.org/10.1016/j.ejca.2013.05.028] [PMID: 23809766]
[10]
Bruix, J.; Qin, S.; Merle, P.; Granito, A.; Huang, Y.H.; Bodoky, G.; Pracht, M.; Yokosuka, O.; Rosmorduc, O.; Breder, V.; Gerolami, R.; Masi, G.; Ross, P.J.; Song, T.; Bronowicki, J.P.; Ollivier-Hourmand, I.; Kudo, M.; Cheng, A.L.; Llovet, J.M.; Finn, R.S.; LeBerre, M.A.; Baumhauer, A.; Meinhardt, G.; Han, G. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet, 2017, 389(10064), 56-66.
[http://dx.doi.org/10.1016/S0140-6736(16)32453-9] [PMID: 27932229]
[11]
Chuma, M.; Terashita, K.; Sakamoto, N. New molecularly targeted therapies against advanced hepatocellular carcinoma: From molecular pathogenesis to clinical trials and future directions. Hepatol. Res., 2015, 45(10), E1-E11.
[http://dx.doi.org/10.1111/hepr.12459] [PMID: 25472913]
[12]
Kudo, M.; Finn, R.S.; Qin, S.; Han, K.H.; Ikeda, K.; Piscaglia, F.; Baron, A.; Park, J.W.; Han, G.; Jassem, J.; Blanc, J.F.; Vogel, A.; Komov, D.; Evans, T.R.J.; Lopez, C.; Dutcus, C.; Guo, M.; Saito, K.; Kraljevic, S.; Tamai, T.; Ren, M.; Cheng, A.L. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: A randomised phase 3 non-inferiority trial. Lancet, 2018, 391(10126), 1163-1173.
[http://dx.doi.org/10.1016/S0140-6736(18)30207-1] [PMID: 29433850]
[13]
Cheng, A.L.; Finn, R.S.; Qin, S.; Han, K.H.; Ikeda, K.; Piscaglia, F.; Kudo, M. Phase III trial of lenvatinib (LEN) vs sorafenib (SOR) in first-line treatment of patients (pts) with unresectable hepatocellular carcinoma (uHCC). J. Clin. Oncol., 2017, 35(15_suppl), 4001-4001.
[14]
Rimassa, L.; Danesi, R.; Pressiani, T.; Merle, P. Management of adverse events associated with tyrosine kinase inhibitors: Improving outcomes for patients with hepatocellular carcinoma. Cancer Treat. Rev., 2019, 77, 20-28.
[http://dx.doi.org/10.1016/j.ctrv.2019.05.004] [PMID: 31195212]
[15]
Cheng, A.L.; Kang, Y.K.; Lin, D.Y.; Park, J.W.; Kudo, M.; Qin, S.; Chung, H.C.; Song, X.; Xu, J.; Poggi, G.; Omata, M.; Pitman Lowenthal, S.; Lanzalone, S.; Yang, L.; Lechuga, M.J.; Raymond, E. Sunitinib versus sorafenib in advanced hepatocellular cancer: Results of a randomized phase III trial. J. Clin. Oncol., 2013, 31(32), 4067-4075.
[http://dx.doi.org/10.1200/JCO.2012.45.8372] [PMID: 24081937]
[16]
Kelley, R.K.; Verslype, C.; Cohn, A.L.; Yang, T.S.; Su, W.C.; Burris, H.; Braiteh, F.; Vogelzang, N.; Spira, A.; Foster, P.; Lee, Y.; Van Cutsem, E. Cabozantinib in hepatocellular carcinoma: Results of a phase 2 placebo-controlled randomized discontinuation study. Ann. Oncol., 2017, 28(3), 528-534.
[http://dx.doi.org/10.1093/annonc/mdw651] [PMID: 28426123]
[17]
Li, Y.; Kasim, V.; Yan, X.; Li, L.; Meliala, I.T.S.; Huang, C.; Li, Z.; Lei, K.; Song, G.; Zheng, X.; Wu, S. Yin Yang 1 facilitates hepatocellular carcinoma cell lipid metabolism and tumor progression by inhibiting PGC-1β-induced fatty acid oxidation. Theranostics, 2019, 9(25), 7599-7615.
[http://dx.doi.org/10.7150/thno.34931] [PMID: 31695789]
[18]
Maeda, O.; Ando, Y. Cabozantinib in hepatocellular carcinoma. N. Engl. J. Med., 2018, 379(14), 1384-1385.
[http://dx.doi.org/10.1056/NEJMc1810178] [PMID: 30285325]
[19]
García, E.R.; Gutierrez, E.A.; Melo, F.C.S.A.D.; Novaes, R.D.; Gonçalves, R.V. Flavonoids effects on hepatocellular carcinoma in murine models: A systematic review. Evid. Based Complement. Altern. Med., 2018, 2018.
[http://dx.doi.org/10.1155/2018/6328970]
[20]
Funakoshi-Tago, M.; Okamoto, K.; Izumi, R.; Tago, K.; Yanagisawa, K.; Narukawa, Y.; Kiuchi, F.; Kasahara, T.; Tamura, H. Anti-inflammatory activity of flavonoids in Nepalese propolis is attributed to inhibition of the IL-33 signaling pathway. Int. Immunopharmacol., 2015, 25(1), 189-198.
[http://dx.doi.org/10.1016/j.intimp.2015.01.012] [PMID: 25614224]
[21]
Holstein, E.; Binder, M.; Mikulits, W. Dynamics of Axl receptor shedding in hepatocellular carcinoma and its implication for theranostics. Int. J. Mol. Sci., 2018, 19(12), 4111.
[http://dx.doi.org/10.3390/ijms19124111] [PMID: 30567378]
[22]
Reichl, P.; Dengler, M.; van Zijl, F.; Huber, H.; Führlinger, G.; Reichel, C.; Sieghart, W.; Peck-Radosavljevic, M.; Grubinger, M.; Mikulits, W. Axl activates autocrine transforming growth factor‐β signaling in hepatocellular carcinoma. Hepatology, 2015, 61(3), 930-941.
[http://dx.doi.org/10.1002/hep.27492] [PMID: 25251599]
[23]
Lee, H.J.; Jeng, Y.M.; Chen, Y.L.; Chung, L.; Yuan, R.H. Gas6/Axl pathway promotes tumor invasion through the transcriptional activation of slug in hepatocellular carcinoma. Carcinogenesis, 2014, 35(4), 769-775.
[http://dx.doi.org/10.1093/carcin/bgt372] [PMID: 24233839]
[24]
Aydin, M.M.; Bayin, N.S.; Acun, T.; Yakicier, M.C.; Akçali, K.C. Role of FLT3 in the proliferation and aggressiveness of hepatocellular carcinoma. Turk. J. Med. Sci., 2016, 46(2), 572-581.
[http://dx.doi.org/10.3906/sag-1501-173] [PMID: 27511526]
[25]
Wang, Y.; Nie, H.; Zhao, X.; Qin, Y.; Gong, X. Bicyclol induces cell cycle arrest and autophagy in HepG2 human hepatocellular carcinoma cells through the PI3K/AKT and Ras/Raf/MEK/ERK pathways. BMC Cancer, 2016, 16(1), 742.
[http://dx.doi.org/10.1186/s12885-016-2767-2] [PMID: 27654866]
[26]
Asati, V.; Mahapatra, D.K.; Bharti, S.K. PI3K/Akt/mTOR and Ras/Raf/MEK/ERK signaling pathways inhibitors as anticancer agents: Structural and pharmacological perspectives. Eur. J. Med. Chem., 2016, 109, 314-341.
[http://dx.doi.org/10.1016/j.ejmech.2016.01.012] [PMID: 26807863]
[27]
Yang, S.; Liu, G. Targeting the Ras/Raf/MEK/ERK pathway in hepatocellular carcinoma. Oncol. Lett., 2017, 13(3), 1041-1047.
[http://dx.doi.org/10.3892/ol.2017.5557] [PMID: 28454211]
[28]
Saha, P.; Talukdar, A.D.; Nath, R.; Sarker, S.D.; Nahar, L.; Sahu, J.; Choudhury, M.D. Role of natural phenolics in hepatoprotection: A mechanistic review and analysis of regulatory network of associated genes. Front. Pharmacol., 2019, 10, 509.
[http://dx.doi.org/10.3389/fphar.2019.00509] [PMID: 31178720]
[29]
Balasundram, N.; Sundram, K.; Samman, S. Phenolic compounds in plants and agri-industrial by-products: Antioxidant activity, occurrence, and potential uses. Food Chem., 2006, 99(1), 191-203.
[http://dx.doi.org/10.1016/j.foodchem.2005.07.042]
[30]
Zhao, J.; Liu, T.; Ma, L.; Yan, M.; Zhao, Y.; Gu, Z.; Huang, Y. Protective effect of acteoside on immunological liver injury induced by Bacillus Calmette-Guerin plus lipopolysaccharide. Planta Med., 2009, 75(14), 1463-1469.
[http://dx.doi.org/10.1055/s-0029-1185796] [PMID: 19548187]
[31]
Lee, K.J.; Woo, E.R.; Choi, C.Y.; Shin, D.W.; Lee, D.G.; You, H.J.; Jeong, H.G. Protective effect of acteoside on carbon tetrachloride-induced hepatotoxicity. Life Sci., 2004, 74(8), 1051-1064.
[http://dx.doi.org/10.1016/j.lfs.2003.07.020] [PMID: 14672760]
[32]
Viswanatha, G.L.; Shylaja, H.; Kishore, D.V.; Venkataranganna, M.V.; Prasad, N.B.L. Acteoside isolated from colebrookea oppositifolia smith attenuates epilepsy in mice via modulation of gamma-aminobutyric acid pathways. Neurotox. Res., 2020, 38(4), 1010-1023.
[http://dx.doi.org/10.1007/s12640-020-00267-0] [PMID: 32803629]
[33]
Chen, B.; McKinley, E.T.; Simmons, A.J.; Ramirez-Solano, M.A.; Zhu, X.; Southard-Smith, A.N.; Markham, N.O.; Sheng, Q.; Drewes, J.L.; Xu, Y. Human colorectal pre-cancer atlas identifies distinct molecular programs underlying two major subclasses of pre-malignant tumors. Biorxiv, 2021.
[http://dx.doi.org/10.1101/2021.01.11.426044]
[34]
Yuan, P.; Fu, C.; Yang, Y.; Adila, A.; Zhou, F.; Wei, X.; Wang, W.; Lv, J.; Li, Y.; Xia, L.; Li, J. Cistanche tubulosa phenylethanoid glycosides induce apoptosis of hepatocellular carcinoma cells by mitochondria-dependent and MAPK pathways and enhance antitumor effect through combination with cisplatin. Integr. Cancer Ther., 2021, 20.
[http://dx.doi.org/10.1177/15347354211013085] [PMID: 33949239]
[35]
Khan, R.A.; Hossain, R.; Roy, P.; Jain, D.; Mohammad Saikat, A.S.; Roy Shuvo, A.P.; Akram, M.; Elbossaty, W.F.; Khan, I.N.; Painuli, S.; Semwal, P.; Rauf, A.; Islam, M.T.; Khan, H. Anticancer effects of acteoside: Mechanistic insights and therapeutic status. Eur. J. Pharmacol., 2022, 916, 174699.
[http://dx.doi.org/10.1016/j.ejphar.2021.174699] [PMID: 34919888]
[36]
Ahmad, M.; Rizwani, G.H.; Aftab, K.; Ahmad, V.U.; Gilani, A.H.; Ahmad, S.P. Acteoside: A new antihypertensive drug. Phytother. Res., 1995, 9(7), 525-527.
[http://dx.doi.org/10.1002/ptr.2650090713]
[37]
Ma, D.; Wang, J.; Liu, L.; Chen, M.; Wang, Z. Acteoside as a potential therapeutic option for primary hepatocellular carcinoma: A preclinical study. BMC Cancer, 2020, 20(1), 936.
[http://dx.doi.org/10.1186/s12885-020-07447-3] [PMID: 32993568]
[38]
Ohno, T.; Inoue, M.; Ogihara, Y.; Saracoglu, I. Antimetastatic activity of acteoside, a phenylethanoid glycoside. Biol. Pharm. Bull., 2002, 25(5), 666-668.
[http://dx.doi.org/10.1248/bpb.25.666] [PMID: 12033512]
[39]
Jing, W.; Chunhua, M.; Shumin, W. Effects of acteoside on lipopolysaccharide-induced inflammation in acute lung injury via regulation of NF-κB pathway in vivo and in vitro. Toxicol. Appl. Pharmacol., 2015, 285(2), 128-135.
[http://dx.doi.org/10.1016/j.taap.2015.04.004] [PMID: 25902336]
[40]
Schapoval, E.E.S.; Winter de Vargas, M.R.; Chaves, C.G.; Bridi, R.; Zuanazzi, J.A.; Henriques, A.T. Antiinflammatory and antinociceptive activities of extracts and isolated compounds from Stachytarpheta cayennensis. J. Ethnopharmacol., 1998, 60(1), 53-59.
[http://dx.doi.org/10.1016/S0378-8741(97)00136-0] [PMID: 9533432]
[41]
Xiong, Q.; Hase, K.; Tezuka, Y.; Tani, T.; Namba, T.; Kadota, S. Hepatoprotective activity of phenylethanoids from Cistanche deserticola. Planta Med., 1998, 64(2), 120-125.
[http://dx.doi.org/10.1055/s-2006-957387] [PMID: 9525102]
[42]
Kim, S.S.; Son, Y.O.; Chun, J.C.; Kim, S.E.; Chung, G.H.; Hwang, K.J.; Lee, J.C. Antioxidant property of an active component purified from the leaves of paraquat-tolerant Rehmannia glutinosa. Redox Rep., 2005, 10(6), 311-318.
[http://dx.doi.org/10.1179/135100005X83734] [PMID: 16438803]
[43]
He, J.; Hu, X.P.; Zeng, Y.; Li, Y.; Wu, H.Q.; Qiu, R.Z.; Ma, W.J.; Li, T.; Li, C.Y.; He, Z.D. Advanced research on acteoside for chemistry and bioactivities. J. Asian Nat. Prod. Res., 2011, 13(5), 449-464.
[http://dx.doi.org/10.1080/10286020.2011.568940] [PMID: 21534045]
[44]
Xiao, Y.; Ren, Q.; Wu, L. The pharmacokinetic property and pharmacological activity of acteoside: A review. Biomed. Pharmacother., 2022, 153, 113296.
[http://dx.doi.org/10.1016/j.biopha.2022.113296] [PMID: 35724511]
[45]
Zhu, J.; Li, G.; Zhou, J.; Xu, Z.; Xu, J. Cytoprotective effects and antioxidant activities of acteoside and various extracts of Clerodendrum cyrtophyllum Turcz leaves against t-BHP induced oxidative damage. Sci. Rep., 2022, 12(1), 12630.
[http://dx.doi.org/10.1038/s41598-022-17038-w] [PMID: 35879416]
[46]
Hanahan, D.; Weinberg, R. A. Hallmarks of cancer: The next generation. cell, 2011, 144(5), 646-674.
[47]
Forner, A.; Da Fonseca, L.G.; Díaz-González, Á.; Sanduzzi-Zamparelli, M.; Reig, M.; Bruix, J. Controversies in the management of hepatocellular carcinoma. JHEP Reports, 2019, 1(1), 17-29.
[http://dx.doi.org/10.1016/j.jhepr.2019.02.003] [PMID: 32039350]
[48]
Hartke, J.; Johnson, M.; Ghabril, M. The diagnosis and treatment of hepatocellular carcinoma. Semin. Diagn. Pathol., 2017, 34(2), 153-159.
[http://dx.doi.org/10.1053/j.semdp.2016.12.011] [PMID: 28108047]
[49]
da Motta Girardi, D.; Correa, T.S.; Crosara Teixeira, M.; Dos Santos Fernandes, G. Hepatocellular carcinoma: Review of targeted and immune therapies. J. Gastrointest. Cancer, 2018, 49(3), 227-236.
[http://dx.doi.org/10.1007/s12029-018-0121-4] [PMID: 29806062]
[50]
Gnoni, A.; Licchetta, A.; Memeo, R.; Argentiero, A.; Solimando, A.G.; Longo, V.; Delcuratolo, S.; Brunetti, O. Role of BRAF in hepatocellular carcinoma: A rationale for future targeted cancer therapies. Medicina (Kaunas), 2019, 55(12), 754.
[http://dx.doi.org/10.3390/medicina55120754] [PMID: 31766556]
[51]
Zuo, Q.; Huang, H.; Shi, M.; Zhang, F.; Sun, J.; Bin, J.; Liao, Y.; Liao, W. Multivariate analysis of several molecular markers and clinicopathological features in postoperative prognosis of hepatocellular carcinoma. Anat. Rec., 2012, 295(3), 423-431.
[http://dx.doi.org/10.1002/ar.21531] [PMID: 22190283]
[52]
Pinato, D.J.; Brown, M.W.; Trousil, S.; Aboagye, E.O.; Beaumont, J.; Zhang, H.; Coley, H.M.; Mauri, F.A.; Sharma, R. Integrated analysis of multiple receptor tyrosine kinases identifies Axl as a therapeutic target and mediator of resistance to sorafenib in hepatocellular carcinoma. Br. J. Cancer, 2019, 120(5), 512-521.
[http://dx.doi.org/10.1038/s41416-018-0373-6] [PMID: 30765873]
[53]
Llovet, J.M.; Montal, R.; Sia, D.; Finn, R.S. Molecular therapies and precision medicine for hepatocellular carcinoma. Nat. Rev. Clin. Oncol., 2018, 15(10), 599-616.
[http://dx.doi.org/10.1038/s41571-018-0073-4] [PMID: 30061739]
[54]
Llovet, J.M.; Villanueva, A.; Lachenmayer, A.; Finn, R.S. Advances in targeted therapies for hepatocellular carcinoma in the genomic era. Nat. Rev. Clin. Oncol., 2015, 12(7), 408-424.
[http://dx.doi.org/10.1038/nrclinonc.2015.103] [PMID: 26054909]
[55]
Mulani, S.K.; Guh, J.H.; Mong, K.K.T. A general synthetic strategy and the anti-proliferation properties on prostate cancer cell lines for natural phenylethanoid glycosides. Org. Biomol. Chem., 2014, 12(18), 2926-2937.
[http://dx.doi.org/10.1039/c3ob42503g] [PMID: 24691797]
[56]
Cheimonidi, C.; Samara, P.; Polychronopoulos, P.; Tsakiri, E.N.; Nikou, T.; Myrianthopoulos, V.; Sakellaropoulos, T.; Zoumpourlis, V.; Mikros, E.; Papassideri, I.; Argyropoulou, A.; Halabalaki, M.; Alexopoulos, L.G.; Skaltsounis, A.L.; Tsitsilonis, O.E.; Aligiannis, N.N.; Trougakos, I.P. Selective cytotoxicity of the herbal substance acteoside against tumor cells and its mechanistic insights. Redox Biol., 2018, 16, 169-178.
[http://dx.doi.org/10.1016/j.redox.2018.02.015] [PMID: 29505920]
[57]
Zhang, Y.; Yuan, Y.; Wu, H.; Xie, Z.; Wu, Y.; Song, X.; Wang, J.; Shu, W.; Xu, J.; Liu, B.; Wan, L.; Yan, Y.; Ding, X.; Shi, X.; Pan, Y.; Li, X.; Yang, J.; Zhao, X.; Wang, L. Effect of verbascoside on apoptosis and metastasis in human oral squamous cell carcinoma. Int. J. Cancer, 2018, 143(4), 980-991.
[http://dx.doi.org/10.1002/ijc.31378] [PMID: 29536537]
[58]
Sitarek, P.; Skała, E.; Toma, M.; Wielanek, M.; Szemraj, J.; Nieborowska-Skorska, M.; Kolasa, M.; Skorski, T.; Wysokińska, H.; Śliwiński, T. A preliminary study of apoptosis induction in glioma cells via alteration of the Bax/Bcl-2-p53 axis by transformed and non-transformed root extracts of Leonurus sibiricus L. Tumour Biol., 2016, 37(7), 8753-8764.
[http://dx.doi.org/10.1007/s13277-015-4714-2] [PMID: 26743778]
[59]
Wu, Y.; Zeng, M.; Xu, R.; Zhang, B.; Wang, S.; Li, B.; Kan, Y.; Cao, B.; Zheng, X.; Feng, W. Inhibitory activity of acteoside in melanoma via regulation of the ERβ-Ras/Raf1-STAT3 pathway. Arch. Biochem. Biophys., 2021, 710, 108978.
[http://dx.doi.org/10.1016/j.abb.2021.108978] [PMID: 34174222]
[60]
Peerzada, K.J.; Faridi, A.H.; Sharma, L.; Bhardwaj, S.C.; Satti, N.K.; Shashi, B.; Tasduq, S.A. Acteoside-mediates chemoprevention of experimental liver carcinogenesis through STAT-3 regulated oxidative stress and apoptosis. Environ. Toxicol., 2016, 31(7), 782-798.
[http://dx.doi.org/10.1002/tox.22089] [PMID: 26990576]
[61]
Jia, W.Q.; Wang, Z.T.; Zou, M.M.; Lin, J.H.; Li, Y.H.; Zhang, L.; Xu, R.X. Verbascoside inhibits glioblastoma cell proliferation, migration and invasion while promoting apoptosis through upregulation of protein tyrosine phosphatase SHP-1 and inhibition of STAT3 phosphorylation. Cell. Physiol. Biochem., 2018, 47(5), 1871-1882.
[http://dx.doi.org/10.1159/000491067] [PMID: 29961065]
[62]
Liu, L.; Cao, Y.; Chen, C.; Zhang, X.; McNabola, A.; Wilkie, D.; Wilhelm, S.; Lynch, M.; Carter, C. Sorafenib blocks the RAF/MEK/ERK pathway, inhibits tumor angiogenesis, and induces tumor cell apoptosis in hepatocellular carcinoma model PLC/PRF/5. Cancer Res., 2006, 66(24), 11851-11858.
[http://dx.doi.org/10.1158/0008-5472.CAN-06-1377] [PMID: 17178882]
[63]
Dimri, M.; Satyanarayana, A. Molecular signaling pathways and therapeutic targets in hepatocellular carcinoma. Cancers, 2020, 12(2), 491.
[http://dx.doi.org/10.3390/cancers12020491] [PMID: 32093152]
[64]
Hsu, C.H.; Huang, Y.H.; Lin, S.M.; Hsu, C. AXL and MET in hepatocellular carcinoma: A systematic literature review. Liver Cancer, 2022, 11(2), 94-112.
[http://dx.doi.org/10.1159/000520501] [PMID: 35634427]
[65]
Wang, Y.; Liu, D.; Zhang, T.; Xia, L. FGF/FGFR signaling in hepatocellular carcinoma: From carcinogenesis to recent therapeutic intervention. Cancers, 2021, 13(6), 1360.
[http://dx.doi.org/10.3390/cancers13061360] [PMID: 33802841]
[66]
Khalaf, H.A.A.; Jasim, R.A.; Ibrahim, I.T. Verbascoside-A review of its antitumor activities. Pharmacol. Pharm., 2021, 12(6), 109-126.
[http://dx.doi.org/10.4236/pp.2021.126011]
[67]
Lu, H.; Qi, Y.; Zhao, Y.; Jin, N. Effects of hydroxyl group on the interaction of carboxylated flavonoid derivatives with S. Cerevisiae α-glucosidase. Curr. Computeraided Drug Des., 2020, 16(1), 31-44.
[http://dx.doi.org/10.2174/1573409914666181022142553] [PMID: 30345924]
[68]
Stockert, A.; Brenneman, M.; Kinder, D.; Mahfouz, T. Docking of select cinnamon components suggest potential for Sirt-1 activation similar to resveratrol. Inter. J. Pharmaceut. Phytopharmacol. Res., 2020, 10(5), 110-121.

Rights & Permissions Print Cite
Article Metrics
37
3
© 2024 Bentham Science Publishers | Privacy Policy