Abstract
This study targeted the production of exopolysaccharide from Bacillus sp. NRC5 grown in Egyptian seawater to use it as natural antitumor therapy. The biological activities of selected exopolysaccharide (BEPS) as an antioxidant, anti-inflammatory and anticancer have been studied. BEPS was evaluated as an anti-inflammatory in vitro against cyclooxygenase (COX-1 and COX-2) and evaluated as an anticancer on human breast and prostate cancer cell lines (MCF-7 and PC3). In addition, BEPS antitumor activity was tested against the Ehrlich Ascites Carcinoma (EAC) model. The BEPS presented potent antioxidant activities, consisted of glucose, mannose, and mannuronic acid in a molar ratio of 1.0:1.7:0.8 with a molecular weight of 3.59 × 105 g/mol. BEPS showed a promising COX-2 inhibitory effect in comparison with the reference drug celecoxib. BEPS appeared efficient anticancer property, where it killed 64.20 and 70.20% of MCF-7 and PC3 cells at 100 µg/ml, respectively (IC50, 76.70, and 70.40 µg/ml, respectively). BEPS exhibited antitumor ability as it prolonged the lifespan of mice to reach 75 days instead of 20 days in the tumor control, reduced viable cancer cells count, tumor volume and weight, modulated blood components, and white blood cells differentiation. BEPS produced from Bacillus sp. NRC5 showed its antioxidant and anti-inflammatory abilities and antitumor abilities, which may all be attributed to its unique composition containing sulfated moieties and uronic acids.
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References
Arena A, Maugeri TL, Pavone B, Iannello D, Gugliandolo C, Bisignano G (2006) Antiviral and immunoregulatory effect of a novel exopolysaccharide from a marine thermotolerant Bacillus licheniformis. Int Immunopharmacol 6:8–13. https://doi.org/10.1016/j.intimp.2005.07.004
Arnao MB, Cano A, Acosta M (2001) The hydrophilic and lipophilic contribution to total antioxidant activity. Food Chem 73:239–244. https://doi.org/10.1016/S0308-8146(00)00324-1
Asirvatham R, Antonysamy A, Rajkumar P, Narayanan L (2012) Anticancer activity of Jasminum angustifolium Linn against Ehrlich ascites carcinoma cells bearing mice. J Exp Integr Med 2:271. https://doi.org/10.5455/jeim.050612.or.031
Boyle CD, Reade AE (1983) Characterization of two extracellular polysaccharides from marine bacteria. Appl Environ Microbiol 46:392–399
Bruce R (1985) An up-and-down procedure for acute toxicity testing. Fundam Appl Toxicol 5:151–157. https://doi.org/10.1016/0272-0590(85)90059-4
Cano A, Arnao MB, Williamson G, Garcia-Conesa MT (2002) Superoxide scavenging by polyphenols: effect of conjugation and dimerization. Redox Rep 7:379–383. https://doi.org/10.1179/135100002125001153
Charlier C, Michaux C (2003) Dual inhibition of COX 2 and 5 LOX as a new strategy to provide safer non steroidal anti inflammatory drugs. Eur J Med Chem 38:645–659. https://doi.org/10.1016/S0223-5234(03)00115-6
Chen R, Liu Z, Zhao J, Chen R, Meng F, Zhang M, Ge W (2011) Antioxidant and immunobiological activity of water-soluble polysaccharide fractions purified from Acanthopanax senticosu. Food Chem 127:434–440
Cipriani TR, Mellinger CG, Souza LM, Baggio CH, Freitas CS, Marques MCA, Gorin PAJ, Sassaki GL, Iacomini M (2008) Acidic heteroxylans from medicinal plants and their anti-ulcer activity. Carbohydr Polym 74:274–278. https://doi.org/10.1016/j.carbpol.2008.02.012
Daba AS, Ezeronye OU (2003) Anticancer effect of polysaccharides isolated from higher basidiomycetes mushrooms. African J Biotechnol 2:835–847. https://doi.org/10.5897/ajb2003.000-1123
Dacie JV, Lewis SM (1975) Laboratory investigation in hemolytic anemia in practical haematology. Practical haematology, 5th edn. Churchill Livingstone, Edinburgh, p 40
Decho AW (1990) Microbial exopolymer secretions in ocean environments: their role(s) in food webs and marine processes. Ocean Mar Annu Rev 28:73–153
Dinis TCP, Madeira VMC, Almeida LM (1994) Action of phenolic derivatives (acetaminophen, salicylate, lipid peroxidation.pdf. Arch Biochem Biophys 315:161–169
Dodgson KS, Price RG (1962) A note on the determination of the ester sulphate content of sulphated polysaccharides. Biochem J 84:106–110. https://doi.org/10.1042/bj0840106
El-Newary SA, Ibrahim AY, Asker MS, Mahmoud MG, El Awady ME (2017) Production, characterization and biological activities of acidic exopolysaccharide from marine Bacillus amyloliquefaciens 3MS 2017. Asian Pac J Trop Med 10(7):652–662. https://doi.org/10.1016/j.apjtm.2017.07.005
Foye WO, Lemke TL (2008) Foye’s principles of medicinal chemistry, 6th edn. Lippincott Williams & Wilkins, Philadelphia
Freitas F, Alves VD, Reis MAM (2011) Advances in bacterial exopolysaccharides: from production to biotechnological applications. Trends Biotechnol 29:388–398. https://doi.org/10.1016/j.tibtech.2011.03.008
Garg R, Kumar R, Nathiya D, Goshain O, Trivedi V, Sharma AK, Murti K (2016) Comparative acute toxicity studies of selected indigenous herbal plants in Swiss albino mice abstract. IOSR J Pharm Biol Sci 11:20–27. https://doi.org/10.9790/3008-1103012027
Ghosh MN (1984) Fundamentals of experimental pharmacology, 2nd edn. Scientific Book Agency, Calcutta, p 1984
Glinsky VV, Raz A (2009) Modified citrus pectin anti-metastatic properties: one bullet, multiple targets. Carbohydr Res 344:1788–1791. https://doi.org/10.1016/j.carres.2008.08.038
Goldmann WH, Sharma AL, Currier SJ, Johnston PD, Rana A, Sharma CP (2001) Saw palmetto berry extract inhibits cell growth and Cox-2 expression in prostatic cancer cells. Cell Biol Int 25:1117–1124. https://doi.org/10.1006/cbir.2001.0779
Gülçin I (2012) Antioxidant activity of food constituents: an overview. Arch Toxicol 86:345–391. https://doi.org/10.1007/s00204-011-0774-2
Gülçin I, Gungor Sat I, Beydemir S, Elmastas M, Kufrevioglu Irfan O (2004) Comparison of antioxidant activity of clove (Eugenia caryophylata Thunb) buds and lavender (Lavandula stoechas L.). Food Chem 87:393–400. https://doi.org/10.1016/j.foodchem.2003.12.008
Guo Z, Xing R, Liu S, Yu H, Wang P, Li C, Li P (2005) The synthesis and antioxidant activity of the Schiff bases of chitosan and carboxymethyl chitosan. Bioorganic Med Chem Lett 15:4600–4603. https://doi.org/10.1016/j.bmcl.2005.06.095
Harrigan WF, McCance ME (1976) Laboratory methods in food dairy and microbiology. Academic Press, New York (204, 267, 209, 308)
Ibrahim AY, Mahmoud MG, Asker MMS (2014) Anti-inflammatory and antioxidant activities of polysaccharide from adansonia digitata: an in vitro study. Int J Pharm Sci Rev Res 25(2):174–182
Jia X, Ding C, Yuan S, Zhang Z, Chen Y, Du L, Yuan M (2014) Extraction, purification and characterization of polysaccharides from Hawk tea. Carbohydr Polym 99:319–324. https://doi.org/10.1016/j.carbpol.2013.07.090
Jun HI, Lee H, Song GS, Kim YS (2006) Characterization of the pectic polysaccharides from pumpkin peel. LWT Food Sci Technol 39:554–561. https://doi.org/10.1016/j.lwt.2005.03.004
Karlapudi AP, Venkateswarulu TC, Srirama K, Kota RK, Mikkili I, Kodali VP (2018) Evaluation of anticancer, anti-microbial and anti-biofilm potential of biosurfactant extracted from an Acinetobacter M6 strain. J King Saud Univ Sci 32:223–227. https://doi.org/10.1016/j.jksus.2018.04.007
Karmakar I, Dolai N, Kumar RBS, Kar B, Roy SN, Haldar PK (2013) Antitumor activity and antioxidant property of Curcuma caesia against Ehrlich’s ascites carcinoma bearing mice. Pharm Biol 51:753–759. https://doi.org/10.3109/13880209.2013.764538
Kim S, Ahu S, Seo W, Kwan G, Park Y (1998) Rheological properties of a novel high viscosity polysaccharide. J Microb Biotech 8:178–181
Kuttan G, Vasudevan DM, Kuttan R (1990) Effect of a preparation from Viscum album on tumor development in vitro and in mice. J Ethnopharmacol 29:35–41. https://doi.org/10.1016/0378-8741(90)90095-B
Larsen LN, Dahl E, Bremer J (1996) Peroxidative oxidation of leuco-dichlorofluorescein. Biochim Biophys Acta 1299:47–53
Liu F, Ooi VE, Chang ST (1997) Free radical scavenging activities of mushroom polysaccharide extracts. Life Sci 60:763–771. https://doi.org/10.1016/S0024-3205(97)00004-0
Lü JM, Lin PH, Yao Q, Chen C (2010) Chemical and molecular mechanisms of antioxidants: experimental approaches and model systems. J Cell Mol Med 14:840–860. https://doi.org/10.1111/j.1582-4934.2009.00897.x
Maidak BL, Olsen GJ, Larson N, Overbeek MJ, Woese CR (1997) The ribosomal database project (RDP). Nucleic Acids Res 25:109–110. https://doi.org/10.1093/nar/25.1.109
Marcocci I, Marguire JJ, Droy-lefaiz MT, Packer L (1994) The nitric oxide-scavenging properties of Ginkgo Biloba. Biochem Biophys Res Commun 201:748–755. https://doi.org/10.1006/bbrc.1994.1764
Martinez J, Moreno JJ (2000) Effect of resveratrol, a natural polyphenolic compound, on reactive oxygen species and prostaglandin production. Biochem Pharmacol 59:865–870. https://doi.org/10.1016/s0006-2952(99)00380-9
Mazumdur UK, Gupta M, Maiti S, Mukherjee D (1997) Antitumor activity of Hydrophilla spinosa on Ehrlich ascites carcinoma and sarcoma-180 induced mice. Indian J Exp Biol 35:473–477
Meng L, Sun S, Li R, Shen Z, Wang P, Jiang X (2015) Antioxidant activity of polysaccharides produced by Hirsutella sp. Carbohydr Polym 117:452–457. https://doi.org/10.1016/j.carbpol.2014.09.076
Methacanon P, Madla S, Kirtikara K, Prasitsil M (2005) Structural elucidation of bioactive fungi-derived polymers. Carbohydr Polym 60:199–203. https://doi.org/10.1016/j.carbpol.2004.12.006
Miller NJ, Rice-Evans CA (1997) The relative contributions of ascorbic acid and phenolic antioxidants to the total antioxidant activity of orange and apple fruit juices and blackcurrant drink. Food Chem 60:331–337. https://doi.org/10.1016/S0308-8146(96)00339-1
Mosmann T (1963) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63. https://doi.org/10.1016/0022-1759(83)90303-4
Onodera Y, Teramura T, Takehara T, Shigi K, Fukuda K (2015) Reactive oxygen species induce Cox-2 expression via TAK1 activation in synovial fibroblast cells. FEBS Open Biol 5:492–501. https://doi.org/10.1016/j.fob.2015.06.001
Oyaizo M (1986) Studies on products of browning reaction: antioxidative activities of products of browning reaction prepared from glucosamine. Jpn J Nutr Diet 44:307–315. https://doi.org/10.5264/eiyogakuzashi.44.307
Reitman S, Frankel SA (1957) Colorimetric method for the determination of serum glutamic oxaloacetic and glutamic pyruvic transaminases. Am J Clin Pathol 28:56–63
Ruch RJ, Cheng SJ, Klaunig JF (1989) Prevention of cytotoxicity and inhibition of intracellular communication by antioxidant catechins isolated from Chinese green tea. Carcinogenesis 10:1003–1008
Salem AAS, Salem MAE, Abbass H (2010) Breast cancer: surgery at the South Egypt cancer Institute. Cancers (basel) 2:1771–1778. https://doi.org/10.3390/cancers2041771
Shene C, Canquil S, Rubilar M (2008) Production of the exopolysaccharides by Streptococcus thermophilus: effect of growth conditions on fermentation kinetics and intrinsic viscosity. Int J Food Microb 124:279–284. https://doi.org/10.1016/j.ijfoodmicro.03.013
Shi Y, Xiong Q, Wang X, Li X, Yu C, Wu J, Yi J, Zhao X, Xu Y, Cui H (2016) Characterization of a novel purified polysaccharide from the flesh of Cipangopaludina chinensis. Carbohydr Polym 136:875–883. https://doi.org/10.1016/j.carbpol.2015.09.062
Sudhamani SR, Tharanathan RN, Prasad MS (2004) Isolation and characterization of an extracellular polysaccharide from Pseudomonas caryophylli CFR 1705. Carbohydr Polym 56:423–427. https://doi.org/10.1016/j.carbpol.2004.03.008
Takase Y, Levesque MH, Luu-The V, El-Alfy M, Labrie F, Pelletier G (2006) Expression of enzymes involved in estrogen metabolism in human prostate. J Histochem Cytochem 54:911–921. https://doi.org/10.1369/jhc.6A6927
Thabrew MI, Hughes RD, McFarlane IG (1997) Screening of hepatoprotective plant components using a HepG2 cell cytotoxicity assay. J Pharm Pharmacol 49:1132–1135. https://doi.org/10.1111/j.2042-7158.1997.tb06055.x
Umezawa H, Okami Y, Kurasawa S, Ohnuki V, Ishizuka M, Takeuchi T, Shiio T, Yugari Y (1983) Marinactan, antitumor polysaccharide produced by marine bacteria. J Antibiot (tokyo) 36:471–475. https://doi.org/10.7164/antibiotics.36.471
Van Pelt LF (1977) Ketamine and xylazine for surgical anesthesia in rats. J Am Vet Med Assoc 171:842–844
Vanhooren PT, Vandamme EJ (1998) Biosynthesis, physiological role use and fermentation process characteristics of bacterial exopolysaccharides. Dev Ferment Bioeng 1:253–300
Wang H, Ooi EV, Ang PO (2007) Antiviral polysaccharides isolated from Hong Kong brown seaweed Hydroclathrus clathratus. Sci China Ser C Life Sci 50:611–618. https://doi.org/10.1007/s11427-007-0086-1
Wang J, Hu S, Nie S, Yu Q, Xie M (2016) Reviews on mechanisms of in vitro antioxidant activity of polysaccharides. 2016: Oxidative Medicine and Cellular Longevity, Article ID 5692852
World Health Organization (2015) Breast cancer: prevention and control. https://www.who.int/cancer/detection/breastcancer/en/. Accessed 6 Sep 2015
Wu H, Min T, Li X, Li L, Lai F, Tang Y, Yang X (2013) Physicochemical properties and antioxidant activities of acidic polysaccharides from wampee seeds. Int J Biol Macromol 59:90–95. https://doi.org/10.1016/j.ijbiomac.2013.04.020
Xing R, Liu S, Guo Z, Yu H, Wang P, Li C, Li Z, Li P (2005) Relevance of molecular weight of chitosan and its derivatives and their antioxidant activities in vitro. Bioorganic Med Chem 13:1573–1577. https://doi.org/10.1016/j.bmc.2004.12.022
Yamaguchi T, Takamura H, Matoba T, Terao J (1998) Hplc method for evaluation of the free radical-scavenging activity of foods by using 1,1-diphenyl-2-picrylhydrazyl. Biosci Biotechnol Biochem 62:1201–1204. https://doi.org/10.1271/bbb.62.1201
Yamaguchi F, Saito M, Ariga T, Yoshimura Y, Nakazawa H (2000) Free radical scavenging activity and antiulcer activity of garcinol from Garcinia indica fruit rind. J Agric Food Chem 48:2320–2325. https://doi.org/10.1021/jf990908c
Zhang HN, Lin ZB (2004) Hypoglycemic effect of Ganoderma lucidum polysaccharides. Acta Pharmacol Sin 25:191–195
Zhang L, Wei L, Takashi N, Hiroshi F (1987) Double-stranded helix of xanthan: rigidity in 0.01M aqueous sodium chloride containing 0.01N hydrochloric acid. Biopolymers 26:333–341. https://doi.org/10.1002/bip.360260303
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The current study was financially supported by National Research Centre, Egypt, through Project no. 12060108 under the title “Discovery of new pharmaceutical raw material for treating prostate diseases.”
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Mohamed, S.S., Ibrahim, A.Y., Asker, M.S. et al. Production, structural and biochemical characterization relevant to antitumor property of acidic exopolysaccharide produced from Bacillus sp. NRC5. Arch Microbiol 203, 4337–4350 (2021). https://doi.org/10.1007/s00203-021-02422-3
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DOI: https://doi.org/10.1007/s00203-021-02422-3