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Current Pharmaceutical Biotechnology

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ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

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Research Article

Cytotoxic and Antibiotic Potential of Secondary Metabolites from the Lichen Umbilicaria muhlenbergii

Author(s): Lyndon Letwin, Ladislav Malek, Zacharias Suntres and Lew Christopher*

Volume 21, Issue 14, 2020

Page: [1516 - 1527] Pages: 12

DOI: 10.2174/1389201021666200504114515

Price: $65

Abstract

Objective: Lichens are emerging as a promising natural source of bioactivities of pharmaceutical interest. The present study aims to contribute to the knowledge of the lichen Umbilicaria muhlenbergii as a potential source of pharmaceutically relevant anticancer and antibiotic lichen chemicals.

Methods: The crude acetone extract of U. muhlenbergii exhibited 13.3 μg mL-1 cytotoxic activity (EC50) against breast cancer cells (MCF-7), as compared to a cisplatin positive control with EC50 of 5.8 μg mL-1. The antibiotic activity of the crude extract against a gram-positive Staphylococcus aureus was 22.5 μg mL-1 as MIC. Using silica gel 60 (SG60) column chromatography, the crude extract was then separated into eight fractions, which were further evaluated for their anticancer activities against MCF-7 cells. By means of propidium iodide flow cytometry, two of the eight SG60 fractions were found to cause cell cycle arrest in MCF-7 cells (73.14% of cells) at the G2 phase, which is indicative of apoptosis and inhibition of cellular proliferation.

Results: Identification of chemical constituents present in these two SG60 fractions was carried out with Thin-Layer Chromatography (TLC) and a lichen metabolite database (Wintabolites). The two fractions (SG60-5 and SG60-6) were found to contain compounds belonging to the chemical families depsides, depsidones, anthraquinones, and xanthones.

Discussion: The SG60-5 and SG60-6 fractions were further fractionated with Sephadex LH-20. Over 15% of the 46 LH-20 fractions obtained from the SG60-5 fraction caused 100% cell death, whereas 32% of the LH-20 fractions derived from SG60 6 fraction reduced cell survival to below 20%.

Conclusion: This work extends the evaluation of the cytotoxic and antibiotic activities of lichen secondary metabolites to the species U. muhlenbergii. It presents encouraging results of pharmaceutical interest that set up lichens as an effective source of new bioactive natural products. Further investigations are underway to reveal the full biopharmaceutical potential of U. muhlenbergii.

Keywords: Lichens, Umbilicaria muhlenbergii, extracts, secondary metabolites, anticancer, antimicrobial.

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[1]
Harvey, A.L.; Gericke, N. Bioprospecting: Creating a value for biodiversity. Research in Biodiversity- Models and Applications; Pavlinov, I., Ed.; InTech: Rijeka, 2011, pp. 323-338.
[2]
Zambare, V.P.; Christopher, L.P. Biopharmaceutical potential of lichens. Pharm. Biol., 2012, 50(6), 778-798.
[http://dx.doi.org/10.3109/13880209.2011.633089] [PMID: 22471936]
[3]
Molnár, K.; Farkas, E. Current results on biological activities of lichen secondary metabolites: A review. Z. Natforsch. C J. Biosci., 2010, 65(3-4), 157-173.
[http://dx.doi.org/10.1515/znc-2010-3-401] [PMID: 20469633]
[4]
Elix, J.; Stocker-Wörgötter, E. Biochemistry and secondary metabolites. Lichen Biol., 1996, 1, 154-180.
[5]
Nash, T.H. Lichen Biology; Cambridge University Press: Cambridge, New York, 2008.
[http://dx.doi.org/10.1017/CBO9780511790478]
[6]
Buçukoglu, T.Z.; Albayrak, S.; Halici, M.G.; Tay, T. Antimicrobial and antioxidant activities of extracts and lichen acids obtained from some Umbilicaria species from Central Anatolia, Turkey. J. Food Process. Preserv., 2013, 37, 1103-1110.
[http://dx.doi.org/10.1111/j.1745-4549.2012.00811.x]
[7]
Manojlovic, N.T.; Vasiljevic, P.J.; Maskovic, P.Z.; Juskovic, M.; Bogdanovic-Dusanovic, G. Chemical composition, antioxidant, and antimicrobial activities of lichen Umbilicaria cylindrica (L.) Delise (Umbilicariaceae). Evid. Based Complement. Alternat. Med., 2012, 2012452431
[http://dx.doi.org/10.1155/2012/452431] [PMID: 21915186]
[8]
Zlatanović, I.; Stanković, M.; Jovanovic, V.S.; Mitić, V.; Zrnzević, I.; Đorđević, A.; Stojanović, G. Biological activities of Umbilicaria crustulosa (Ach.) Frey acetone extract. J. Serb. Chem. Soc., 2017, 82, 41-150.
[http://dx.doi.org/10.2298/JSC161019014Z]
[9]
Kosanić, M.; Ranković, B.; Stanojković, T. Antioxidant, antimicrobial, and anticancer activity of 3 Umbilicaria species J. Food Sci., , 2012, 77, 1-T20.
[10]
Richardson, D.; Niebger, E.; Lavoie, P.; Padovan, D. Anion accumulation by lichens I. The characteristics and kinetics of arsenate uptake by Umbilicaria muhlenbergii. New Phytol., 1984, 96, 71-82.
[http://dx.doi.org/10.1111/j.1469-8137.1984.tb03544.x]
[11]
Instructions 56-1190-97 AD, Gel Filtration, Sephadex LH-20; AB GHB-S, Ed; General Electric Company: Uppsala: Sweden, 2006, p. 11.
[12]
Mietzsch, E.; Lumbsch, H.; Elix, J. Wintabolites (Mactabolites for Windows); Users manual and computer program; University Essen: Essen, 1994.
[13]
Schmeda-Hirschmann, G.; Tapia, A.; Lima, B.; Pertino, M.; Sortino, M.; Zacchino, S.; Arias, A.R.; Feresin, G.E. A new antifungal and antiprotozoal depside from the Andean lichen Protousnea poeppigii. Phytother. Res., 2008, 22(3), 349-355.
[http://dx.doi.org/10.1002/ptr.2321] [PMID: 18058986]
[14]
Millot, M.; Tomasi, S.; Studzinska, E.; Rouaud, I.; Boustie, J. Cytotoxic constituents of the lichen Diploicia canescens. J. Nat. Prod., 2009, 72(12), 2177-2180.
[http://dx.doi.org/10.1021/np9003728] [PMID: 19919064]
[15]
Millot, M.; Tomasi, S.; Articus, K.; Rouaud, I.; Bernard, A.; Boustie, J. Metabolites from the Lichen Ochrolechia parella growing under two different heliotropic conditions. J. Nat. Prod., 2007, 70(2), 316-318.
[http://dx.doi.org/10.1021/np060561p] [PMID: 17256903]
[16]
Kinoshita, K.; Togawa, T.; Hiraishi, A.; Nakajima, Y.; Koyama, K.; Narui, T.; Wang, L.S.; Takahashi, K. Antioxidant activity of red pigments from the lichens Lethariella sernanderi, L. cashmeriana, and L. sinensis. J. Nat. Med., 2010, 64(1), 85-88.
[http://dx.doi.org/10.1007/s11418-009-0364-2] [PMID: 19802654]
[17]
Hu, L-H. Yip, S.-C.; Sim, K.-Y. Xanthones from Hypericum ascyron. Phytochemistry, 1999, 52, 1371-1373.
[http://dx.doi.org/10.1016/S0031-9422(99)00412-4]
[18]
Okoye, F.B.C.; Lu, S.; Nworu, C.S.; Esimone, C.O.; Proksch, P.; Chadli, A.; Debbab, A. Depsidone and diaryl ether derivatives from the fungus Corynespora cassiicola, an endophyte of Gongronema latifolium. Tetrahedron Lett., 2013, 54, 4210-4214.
[http://dx.doi.org/10.1016/j.tetlet.2013.05.117]
[19]
Sultana, N.; Afolayan, A.J. A new depsidone and antibacterial activities of compounds from Usnea undulata Stirton. J. Asian Nat. Prod. Res., 2011, 13(12), 1158-1164.
[http://dx.doi.org/10.1080/10286020.2011.622720] [PMID: 22115039]
[20]
Institute CaLS. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically 11th ed.; 1-56238 836-3,; , 2018.
[21]
Yeash, E.A.; Letwin, L.; Malek, L.; Suntres, Z.; Knudsen, K.; Christopher, L.P. Biological activities of undescribed North American lichen species. J. Sci. Food Agric., 2017, 97(14), 4721-4726.
[http://dx.doi.org/10.1002/jsfa.8340] [PMID: 28369962]
[22]
Schmidt, B.; Ribnicky, D.M.; Poulev, A.; Logendra, S.; Cefalu, W.T.; Raskin, I. A natural history of botanical therapeutics. Metabolism, 2008, 57(7)(Suppl. 1), S3-S9.
[http://dx.doi.org/10.1016/j.metabol.2008.03.001] [PMID: 18555851]
[23]
Verma, S.P.; Salamone, E.; Goldin, B. Curcumin and genistein, plant natural products, show synergistic inhibitory effects on the growth of human breast cancer MCF-7 cells induced by estrogenic pesticides. Biochem. Biophys. Res. Commun., 1997, 233(3), 692-696.
[http://dx.doi.org/10.1006/bbrc.1997.6527] [PMID: 9168916]
[24]
Harvey, A.L. Natural products in drug discovery. Drug Discov. Today, 2008, 13(19-20), 894-901.
[http://dx.doi.org/10.1016/j.drudis.2008.07.004] [PMID: 18691670]
[25]
Laxminarayan, R.; Duse, A.; Wattal, C.; Zaidi, A.K.; Wertheim, H.F.; Sumpradit, N.; Vlieghe, E.; Hara, G.L.; Gould, I.M.; Goossens, H.; Greko, C.; So, A.D.; Bigdeli, M.; Tomson, G.; Woodhouse, W.; Ombaka, E.; Peralta, A.Q.; Qamar, F.N.; Mir, F.; Kariuki, S.; Bhutta, Z.A.; Coates, A.; Bergstrom, R.; Wright, G.D.; Brown, E.D.; Cars, O. Antibiotic resistance-the need for global solutions.Lancet Infect. Dis., , 2013, 13(12), 1057-1098.
[http://dx.doi.org/10.1016/S1473-3099(13)70318-9] [PMID: 24252483]
[26]
Sharma, V.K.; Johnson, N.; Cizmas, L.; McDonald, T.J.; Kim, H. A review of the influence of treatment strategies on antibiotic resistant bacteria and antibiotic resistance genes.Chemosphere,, 2016, 150, 702-714.
[http://dx.doi.org/10.1016/j.chemosphere.2015.12.084]
[27]
Valadbeigi, T.; Bahrami, A.M.; Shaddel, M. Antibacterial and antifungal activities of different lichens extracts. Eur. J. Clin. Microbiol. Infect. Dis., 2014, 2, 71-75.
[28]
Shrestha, G.; Raphael, J.; Leavitt, S.D.; St Clair, L.L. In vitro evaluation of the antibacterial activity of extracts from 34 species of North American lichens. Pharm. Biol., 2014, 52(10), 1262-1266.
[http://dx.doi.org/10.3109/13880209.2014.889175] [PMID: 24863278]
[29]
Cankiliç, M.Y.; Sariözlü, N.Y.; Mehmet, C.; Tay, F. Screening of antibacterial, antituberculosis and antifungal effects of lichen Usnea florida and its thamnolic acid constituent. Biomed. Res. (Aligarh), 2017, 28(7), 3108-3113.
[30]
Neff, G.W.; Reddy, K.R.; Durazo, F.A.; Meyer, D.; Marrero, R.; Kaplowitz, N. Severe hepatotoxicity associated with the use of weight loss diet supplements containing ma huang or usnic acid. J. Hepatol., 2004, 41(6), 1062-1064.
[http://dx.doi.org/10.1016/j.jhep.2004.06.028] [PMID: 15582145]
[31]
Guo, L.; Shi, Q.; Fang, J.L.; Mei, N.; Ali, A.A.; Lewis, S.M.; Leakey, J.E.; Frankos, V.H. Review of usnic acid and Usnea barbata toxicity. J. Environ. Sci. Health C Environ. Carcinog. Ecotoxicol. Rev., 2008, 26(4), 317-338.
[http://dx.doi.org/10.1080/10590500802533392] [PMID: 19034791]
[32]
Kaufmann, S.H.; Earnshaw, W.C. Induction of apoptosis by cancer chemotherapy. Exp. Cell Res., 2000, 256(1), 42-49.
[http://dx.doi.org/10.1006/excr.2000.4838] [PMID: 10739650]
[33]
Correché, E.R.; Enriz, R.D.; Piovano, M.; Garbarino, J.; Gómez-Lechón, M.J. Cytotoxic and apoptotic effects on hepatocytes of secondary metabolites obtained from lichens. Altern. Lab. Anim., 2004, 32(6), 605-615.
[http://dx.doi.org/10.1177/026119290403200611] [PMID: 15757498]
[34]
Russo, A.; Piovano, M.; Lombardo, L.; Garbarino, J.; Cardile, V. Lichen metabolites prevent UV light and nitric oxide-mediated plasmid DNA damage and induce apoptosis in human melanoma cells. Life Sci., 2008, 83(13-14), 468-474.
[http://dx.doi.org/10.1016/j.lfs.2008.07.012] [PMID: 18721817]
[35]
Brisdelli, F.; Perilli, M.; Sellitri, D.; Piovano, M.; Garbarino, J.A.; Nicoletti, M.; Bozzi, A.; Amicosante, G.; Celenza, G. Cytotoxic activity and antioxidant capacity of purified lichen metabolites: An in vitro study. Phytother. Res., 2013, 27(3), 431-437.
[http://dx.doi.org/10.1002/ptr.4739] [PMID: 22628260]
[36]
Bačkorová, M.; Jendželovský, R.; Kello, M.; Bačkor, M.; Mikeš, J.; Fedoročko, P. Lichen secondary metabolites are responsible for induction of apoptosis in HT-29 and A2780 human cancer cell lines. Toxicol. In Vitro, 2012, 26(3), 462-468.
[http://dx.doi.org/10.1016/j.tiv.2012.01.017] [PMID: 22285236]

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