In the present study, we aimed to evaluate the anticancer activities of Cetraria islandica (C.islandica) extracts on MCF-7 breast cancer cell lines. Cell viability, protein levels, apoptotic cells number, F-actin distribution were measured. Cell viability of MCF-7 breast cancer cells was found to be reduced in a dose-dependent manner.EC50 values of C.islandica on MCF-7 cells were found to be 9.2047 E-5 g/ml (cell amount) by using intelligence system. Expressions of p53, caspase 3 and Bcl-2, were shown to be elevated after low doses of extract and diminished after high dose treatments. PPAR- protein level was decreased, although AMP-activated kinases-α1 (AMPK-α1) protein level was increasedin its extract groups. ERK1/2 protein level was also elevated in its extract groups. 125 mg/ml of extract treated cells show a low decrease in actin filament density. MCF-7 cells with C.islandica treatment for 24 h increased the apoptotic cell percentage, though the cells-treated with C.islandica for 48 was high necrotic cells percentage. Consequently, the C.islandica extract treatment causes to elevate ERK1/2 and AMPK-α1 protein levels, resulting in PPAR- and then triggers the apoptosis by modulation caspase-3 and P53 protein levels. Therefore, C.islandica might be a good candidate for anticancer tissue, especially soft tissue tumours.
___
Bakker JL, Wever K, van Waesberghe JH, Beeker A, Meijers- Heijboer H, Konings IR, Verheul HM. 2015. What is the benefit of treatment with multiple lines of chemotherapy for patients with metastatic breast cancer? A retrospective cohort study. Cancer Epidemiol, 39(6): 848-853. doi:10.1016/j.canep.2015.09.010
Bessadottir M, Eiriksson FF, Becker S, Ogmundsdottir MH, Omarsdottir S, Thorsteinsdottir M, Ogmundsdottir HM. 2015. Anti-proliferative and pro-apoptotic effects of lichenderived compound protolichesterinic acid are not mediated by its lipoxygenase-inhibitory activity. Prostaglandins Leukot Essent Fatty Acids, 98: 39-47. doi:10.1016/j.plefa. 2015.04.009
Bontempo P, De Masi L, Carafa V, Rigano D, Scisciola L, Iside, C, Altucci L. 2015. Anticancer activities of anthocyanin extract from genotyped Solanum tuberosum L. “Vitelotte”. Journal of Functional Foods, 19: 584-593. doi:10.1016/j.jff. 2015.09.063
Carling D, Thornton C, Woods A, Sanders MJ. 2012. AMPactivated protein kinase: new regulation, new roles? Biochem J, 445(1): 11-27. doi:10.1042/BJ20120546
Colak S, Geyikoglu F, Turkez H, Bakir TO, Aslan A. 2013. The ameliorative effect of Cetraria islandica against diabetesinduced genetic and oxidative damage in human blood. Pharm Biol, 51(12): 1531-1537. doi:10.3109/13880209. 2013.801994
Coskun ZM, Ersoz M, Acikgoz B, Karalti I, Cobanoglu G, Sesal C. 2015. Anti-Proliferative and Apoptotic Effects of Methanolic Extracts from Different Cladonia Species on Human Breast Cancer Cells. Folia Biol (Praha), 61(3): 97- 103.
Çelikler Kasimoğulları, S, Oran S, Ari F, Ulukaya E, Aztopal N, Sarimahmut M, Öztürk Ş. 2014. Genotoxic, cytotoxic, and apoptotic effects of crude extract of Usnea filipendula Stirt. in vitro. Turkish Journal of Biology, 38: 940-947. doi:10.3906/biy-1405-23
Fernandez-Moriano C, Divakar PK, Crespo A, Gomez- Serranillos MP. 2015. Neuroprotective activity and cytotoxic potential of two Parmeliaceae lichens: Identification of active compounds. Phytomedicine, 22(9): 847-855. doi:10.1016/j.phymed.2015.06.005
Gulcin I, Oktay M, Kufrevioglu OI, Aslan A. 2002. Determination of antioxidant activity of lichen Cetraria islandica (L) Ach. J Ethnopharmacol, 79(3): 325-329.
Guo H, Sun S, Zhang X, Zhang XJ, Gao L, Zhao JJ. 2010. AMPK enhances the expression of pancreatic duodenal homeobox-1 via PPARalpha, but not PPARgamma, in rat insulinoma cell line INS-1. Acta Pharmacol Sin, 31(8): 963- 969. doi:10.1038/aps.2010.78
Guven C, Taskin E, Akcakaya H. 2016. Melatonin Prevents Mitochondrial Damage Induced by Doxorubicin in Mouse Fibroblasts Through Ampk-Ppar Gamma-Dependent Mechanisms. Med Sci Monit, 22: 438-446.
Hadrich F, Garcia M, Maalej A, Moldes M, Isoda H, Feve B, Sayadi S. 2016. Oleuropein activated AMPK and induced insulin sensitivity in C2C12 muscle cells. Life Sci, 151: 167-173. doi:10.1016/j.lfs.2016.02.027
He X, Hu Y, Winter J, Young GP. 2010. Anti-mutagenic lichen extract has double-edged effect on azoxymethane-induced colorectal oncogenesis in C57BL/6J mice. Toxicology Mechanisms and Methods, 20(1): 31-35. doi:10.3109/15376510903521232
Herrera CL, Kim DY, Kumar SR, Bryan JN. 2015. Peroxisome proliferator activated receptor γ protein expression is asymmetrically distributed in primary lung tumor and metastatic to lung osteosarcoma samples and does not correlate with gene methylation. BMC Veterinary Research, 11(1). doi:10.1186/s12917-015-0547-x
Hoskin PJ, Diez P, Gallop-Evans E, Syndikus I, Bates A, Bayne, M. 2016. Recommendations for Radiotherapy Technique and Dose in Extra-nodal Lymphoma. Clin Oncol (R Coll Radiol), 28(1): 62-68. doi:10.1016/j.clon.2015.09.005
Kartnig T. 1987. Cetraria islandica - Islandisches Moos. Z. Phytotherapy, 8: 127-130.
Khazir J, Mir BA, Pilcher L, Riley DL. 2014. Role of plants in anticancer drug discovery. Phytochemistry Letters, 7: 173- 181. doi:10.1016/j.phytol.2013.11.010
Kodiha M, Rassi JG, Brown CM, Stochaj U. 2007. Localization of AMP kinase is regulated by stress, cell density, and signaling through the MEK-->ERK1/2 pathway. Am J Physiol Cell Physiol, 293(5): C1427-1436. doi:10.1152/ajpcell.00176.2007
Kole L, Sarkar M, Deb A, Giri B. 2016. Pioglitazone, an antidiabetic drug requires sustained MAPK activation for its anti-tumor activity in MCF7 breast cancer cells, independent of PPAR-gamma pathway. Pharmacol Rep, 68(1): 144-154. doi:10.1016/j.pharep.2015.08.001
Kosanic M, Manojlovic N, Jankovic S, Stanojkovic T, Rankovic B. 2013. Evernia prunastri and Pseudoevernia furfuraceae lichens and their major metabolites as antioxidant, antimicrobial and anticancer agents. Food Chem Toxicol, 53: 112-118. doi:10.1016/j.fct.2012.11.034
Kosanić M, Ranković B, Stanojković T, Rančić A, Manojlović, N. 2014. Cladonia lichens and their major metabolites as possible natural antioxidant, antimicrobial and anticancer agents. LWT - Food Science and Technology, 59(1): 518- 525. doi:10.1016/j.lwt.2014.04.047
Lu Z, Xu S. 2006. ERK1/2 MAP kinases in cell survival and apoptosis. IUBMB Life, 58(11): 621-631. doi:10.1080/15216540600957438
Manola J, Royston P, Elson P, McCormack JB, Mazumdar M, Negrier S. 2011. Prognostic model for survival in patients with metastatic renal cell carcinoma: results from the international kidney cancer working group. Clin Cancer Res, 17(16): 5443-5450. doi:10.1158/1078-0432.CCR-11-0553
Mebratu Y, Tesfaigzi Y. 2009. How ERK1/2 activation controls cell proliferation and cell death: Is subcellular localization the answer? Cell Cycle, 8(8): 1168-1175. doi:10.4161/cc.8.8.8147
Nikhil K, Sharan S, Singh AK, Chakraborty A, Roy P. 2014. Anticancer activities of pterostilbene-isothiocyanate conjugate in breast cancer cells: involvement of PPARgamma. PLoS One, 9(8): e104592. doi:10.1371/ journal.pone.0104592
Nishimoto S, Nishida E. 2006. MAPK signalling: ERK5 versus ERK1/2. EMBO Rep, 7(8): 782-786. doi:10.1038/ sj.embor.7400755
Olafsdottir ES, Ingolfsdottir K, Barsett H, Paulsen BS, Jurcic, K, Wagner H. 1999. Immunologically active (1-->3)-(1-->4)- alpha-D-glucan from Cetraria islandica. Phytomedicine, 6(1): 33-39.
Remila S, Atmani-Kilani D, Delemasure S, Connat JL, Azib L, Richard T, Atmani D. 2015. Antioxidant, cytoprotective, anti-inflammatory and anticancer activities of Pistacia lentiscus (Anacardiaceae) leaf and fruit extracts. European Journal of Integrative Medicine, 7(3): 274-286. doi:10.1016/j.eujim.2015.03.009
Roleira FM, Tavares-da-Silva EJ, Varela CL, Costa SC, Silva T, Garrido J, Borges F. 2015. Plant derived and dietary phenolic antioxidants: anticancer properties. Food Chem, 183: 235-258. doi:10.1016/j.foodchem.2015.03.039
Sakharkar MK, Shashni B, Sharma K, Dhillon SK, Ranjekar PR, Sakharkar KR. 2013. Therapeutic Implications of Targeting Energy Metabolism in Breast Cancer. PPAR Research, 2013, 1-11. doi:10.1155/2013/109285
Shweta S, Gurumurthy BR, Ravikanth G, Ramanan US, Shivanna MB. 2013. Endophytic fungi from Miquelia dentata Bedd., produce the anti-cancer alkaloid, camptothecine. Phytomedicine, 20(3-4): 337-342. doi:10.1016/j.phymed.2012.11.015
Sozio MS, Lu C, Zeng Y, Liangpunsakul S, Crabb DW. 2011. Activated AMPK inhibits PPAR-{alpha} and PPAR- {gamma} transcriptional activity in hepatoma cells. Am J Physiol Gastrointest Liver Physiol, 301(4): G739-747. doi:10.1152/ajpgi.00161.2011
Tagne RS, Telefo BP, Nyemb JN, Yemele DM, Njina SN, Goka SM, Farooq AD. 2014. Anticancer and antioxidant activities of methanol extracts and fractions of some Cameroonian medicinal plants. Asian Pac J Trop Med, 7S1: 442-447. doi:10.1016/S1995-7645(14)60272-8
Unnati Shah RS, Sanjeev A, Niyati A. 2013. Novel anticancer agents from plant sources Chinese Journal of Natural Medicines, 11(1): 16-23. doi:10.1016/S1875- 5364(13)60002-3
Vaithiyanathan V, Mirunalini S. 2016. Assessment of anticancer activity: A comparison of dose–response effect of ethyl acetate and methanolic extracts of Pergularia daemia (Forsk). Oral Science International, 13(1): 24-31. doi:10.1016/s1348-8643(15)00039-7
Xu M, Heidmarsson S, Olafsdottir ES, Buonfiglio R, Kogej T, Omarsdottir S. 2016. Secondary metabolites from cetrarioid lichens: Chemotaxonomy, biological activities and pharmaceutical potential. Phytomedicine, 23(5): 441-459. doi:10.1016/j.phymed.2016.02.012
Yan T, Zhao Y, Zhang X, Lin X. 2016. Astaxanthin Inhibits Acetaldehyde-Induced Cytotoxicity in SH-SY5Y Cells by Modulating Akt/CREB and p38MAPK/ERK Signaling Pathways. Mar Drugs, 14(3). doi:10.3390/md14030056
Yang C, Nguyen TT, Yoon S, Yang Y, Lee HB, Oh S, Kim H. 2014. Lichen Secondary Metabolites in Flavocetraria cucullata Exhibit Anti-Cancer Effects on Human Cancer Cells through the Induction of Apoptosis and Suppression of Tumorigenic Potentials. PLoS One, 9(10): e111575. doi:10.1371/journal.pone.0111575
Yen CS, Chen JC, Chang YF, Hsu YF, Chiu PT, Shiue C, Hsu MJ. 2016. Lovastatin causes FaDu hypopharyngeal carcinoma cell death via AMPK-p63-survivin signaling cascade. Sci Rep, 6: 25082. doi:10.1038/srep25082
Zhang HA, Yang XY, Xiao YF. 2016. AMPKalpha1 overexpression alleviates the hepatocyte model of nonalcoholic fatty liver disease via inactivating p38MAPK pathway. Biochem Biophys Res Commun, 474(2): 364-370. doi:10.1016/j.bbrc.2016.04.111