Eckol, a potential inhibitor of aryl hydrocarbon receptor, inhibits proliferation and induces apoptosis in breast cancer cells
DOI:
https://doi.org/10.3329/bjp.v17i3.60353Keywords:
Apoptosis, AhR, Breast cancer, Docking study, EckolAbstract
The present study was designed to explore phlorotannin eckol protein targets and evaluate the anti-cancer effects of eckol against human breast cancer cells. ProTox-II server and protein-ligand docking analysis deter-mined the aryl hydrocarbon receptor (AhR) as a putative target of eckol. The AhR has been determined as a potential target for breast cancer treatment. The effect of eckol treatment on proliferation, apoptosis, and cell cycle activities was detected in MDA-MB-231 and SK-BR-3 breast cancer cell lines which were selected dependent on AhR expression profiles. Consistent with the AhR expression profile, MDA-MB-231 cells were more sensitive to eckol treatment compared to SK-BR-3 cells in proliferation, apoptosis and cell cycle results. Eckol treatment shows a significant antiproliferative and apoptotic response in breast cancer cells. Overall, these results indicated that the action of eckol may be related to the AhR gene regulation in different breast cancer cell lines.
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Baker JR, Sakoff JA, McCluskey A. The aryl hydrocarbon receptor (AhR) as a breast cancer drug target. Med Res Rev. 2020; 40: 972-1001.
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, 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: 394-424.
Buyel J. F. Plants as sources of natural and recombinant anti-cancer agents. Biotechnol Adv. 2018; 36: 506-20.
Cardoso F, Harbeck N, Barrios CH, Bergh J, Cortés J, El Saghir N, Francis PA, Hudis CA, Ohno S, Partridge AH, Sledge GW. Research needs in breast cancer. Ann Oncol. 2017; 28: 208-17.
Corrada D, Soshilov AA, Denison MS, Bonati L. Deciphering dimerization modes of PAS domains: Computational and experimental analyses of the AhR: ARNT complex reveal new insights into the mechanisms of AhR transformation. PLoS Comput Biol. 2016; 12: e1004981.
Demain AL, Vaishnav P. Natural products for cancer chemotherapy. Microb Biotechnol. 2011; 4: 687-99.
Dyshlovoy SA, Honecker F. Marine compounds and cancer: Where do we stand? Mar Drugs. 2015; 13: 5657-65.
Fisusi FA, Akala EO. Drug combinations in breast cancer therapy. Pharm Nanotechnol. 2019; 7: 3-23.
Gilbert J, De Iuliis GN, Tarleton M, McCluskey A, Sakoff JA. (Z)-2-(3, 4-Dichlorophenyl)-3-(1H-pyrrol-2-yl) acrylonitrile exhibits selective antitumor activity in breast cancer cell lines via the aryl hydrocarbon receptor pathway. Mol Pharmacol. 2018; 93: 168-77.
Jun YJ, Lee M, Shin T, Yoon N, Kim JH, Kim HR. Eckol enhances heme oxygenase-1 expression through activation of Nrf2/JNK pathway in HepG2 cells. Molecules 2014; 19: 15638-52.
Kim AD, Kang KA, Piao MJ, Kim KC, Zheng J, Yao CW, Cha JW, Hyun CL, Kang HK, Lee NH, Hyun JW. Cytoprotective effect of Eckol against oxidative stress‐induced mitochondrial dysfunction: Involvement of the Foxo3a/Ampk path-way. J Cell Biochem. 2014; 115: 1403-11.
Kozak A, Unal D, Tuney-Kizilkaya I. Seasonal variations of epiphytic flora, abscisic acid production and physiological response in the brown alga Cystoseira foeniculacea (Linnaeus) Greville. Cah Biol Mar. 2020; 61: 169-79.
Li ZD, Wang K, Yang XW, Zhuang ZG, Wang JJ, Tong XW. Expression of aryl hydrocarbon receptor in relation to p53 status and clinicopathological parameters in breast cancer. Int J Clin Exp Pathol. 2014; 7: 7931.
Manandhar B, Paudel P, Seong SH, Jung HA, Choi JS. Characterizing eckol as a therapeutic aid: A systematic review. Mar Drugs. 2019; 17: 361.
Martínez Andrade KA, Lauritano C, Romano G, Ianora A. Marine microalgae with anti-cancer properties. Mar Drugs. 2018; 16: 165.
Mohamed HT, Gadalla R, El-Husseiny N, Hassan H, Wang Z, Ibrahim SA, El-Shinawi M, Sherr DH, Mohamed MM. Inflammatory breast cancer: Activation of the aryl hydrocarbon receptor and its target CYP1B1 correlates closely with Wnt5a/b-β-catenin signalling, the stem cell phenotype and disease progression. J Adv Res. 2019; 16: 75-86.
Moretti S, Nucci N, Menicali E, Morelli S, Bini V, Colella R, Mandarano M, Sidoni A, Puxeddu E. The aryl hydrocarbon receptor is expressed in thyroid carcinoma and appears to mediate epithelial-mesenchymal-transition. Cancers 2020; 12: 145.
Mwangi HM, Njue WM, Onani MO, Thovhoghi N, Mabusela WT. Phlorotannins and a sterol isolated from a brown alga Ecklonia maxima, and their cytotoxic activity against selected cancer cell lines HeLa, H157 and MCF7. Interdiscip J Chem. 2017; 2: 1-6.
Paris A, Tardif N, Galibert MD, Corre S. AhR and cancer: From gene profiling to targeted therapy. Int J Mol Sci. 2021; 22: 752.
Pawar SS, Rohane SH. Review on discovery studio: An important tool for molecular docking. Asian J Res Chem. 2021; 14: 86-88.
Piao MJ, Lee NH, Chae S, Hyun JW. Eckol inhibits ultraviolet B-induced cell damage in human keratinocytes via a decrease in oxidative stress. Biol Pharm Bull. 2012; 35: 873-80.
Picot MC, Bender O, Atalay A, Zengin G, Loffredo L, Hadji-Minaglou F, Mahomoodally MF. Multiple pharmacological targets, cytotoxicity, and phytochemical profile of Aphloia theiformis (Vahl.) Benn. Biomed Pharmacother. 2017; 89: 342-50.
Powell JB, Goode GD, Eltom SE. The aryl hydrocarbon receptor: A target for breast cancer therapy. J Cancer Ther. 2013; 4: 1177.
Rajan DK, Mohan K, Zhang S, Ganesan AR. Dieckol: A brown algal phlorotannin with biological potential. Biomed Pharmacother. 2021; 142: 111988.
Rieger AM, Nelson KL, Konowalchuk JD, Barreda DR. Modified annexin V/propidium iodide apoptosis assay for accurate assessment of cell death. JoVE. 2011; 2011.
Seeliger D, de Groot BL. Ligand docking and binding site analysis with PyMOL and Autodock/Vina. J Comput Aided Mol Des. 2010; 24: 417-22.
Stanford EA, Ramirez-Cardenas A, Wang Z, Novikov O, Alamoud K, Koutrakis P, Mizgerd JP, Genco CA, Kukuruzinska M, Monti S, Bais MV. Role for the aryl hydrocarbon receptor and diverse ligands in oral squamous cell carcinoma migration and tumorigenesis: Role of the AhR in oral cancer migration and tumorigenesis. Mol Cancer Res. 2016; 14: 696-706.
Su JM, Lin P, Chang H. Prognostic value of nuclear translocation of aryl hydrocarbon receptor for non-small cell lung cancer. Anti-cancer Res. 2013; 33: 3953-61.
Vacher S, Castagnet P, Chemlali W, Lallemand F, Meseure D, Pocard M, Bieche I, Perrot-Applanat M. High AHR expression in breast tumors correlates with expression of genes from several signaling pathways namely inflammation and endogenous tryptophan metabolism. PloS One. 2018; 13: e0190619.
Waks AG, Winer EP. Breast cancer treatment: A review. JAMA. 2019; 321: 288-300.
Yao, XY, Bai Q. Taraxerol protects the human hepatic L02 cells from hydrogen peroxide-induced apoptosis. Bangladesh J Pharmacol. 2017; 12: 133-39.
Yersal O, Barutca S. Biological subtypes of breast cancer: Prognostic and therapeutic implications. World J Clin Oncol. 2014; 5: 412.
Zhang C, Li X, Kim SK. Application of marine biomaterials for nutraceuticals and functional foods. Food Sci Biotechnol. 2012; 21: 625-31.
Zhang M, Zhou W, Zhao S, Li S, Yan D, Wang J. Eckol inhibits Reg3A-induced proliferation of human SW1990 pancreatic cancer cells. Exp Ther Med. 2019; 18: 2825-32.
Zhang R, Kang KA, Piao MJ, Ko DO, Wang ZH, Lee IK, Kim BJ, Jeong IY, Shin T, Park JW, Lee NH. Eckol protects V79-4 lung fibroblast cells against γ-ray radiation-induced apoptosis via the scavenging of reactive oxygen species and inhibiting of the c-Jun NH2-terminal kinase pathway. Eur J Pharmacol. 2008; 591: 114-23.
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