Enteromorpha Compressa, Gelidium pulchrum, Macro algae from Egypt Exhibit Potent Anticancer, Antioxidant and anti-inflammatory Activities
Keywords:
Gelidium pulchrum, Enteromorpha compressa, Anticancer, Apoptosis, Antioxidant, Anti- inflammatory ActivitiesAbstract
Over the past several decades, algae and their extracts have generated an enormous amount of interest in the pharmaceutical industry as a fresh source of bioactive compounds. The aim of this work was to evaluate anticancer, antioxidant and anti-inflammatory properties of absolute and aqueous (50%) methanol extracts of both Gelidium pulchrum and Enteromorpha compressa algae. In vitro cytotoxicity of the extracts was tested by MTT and trypan blue technique against two malignant cell lines (HeLa and EACC). The effect of methanol extracts on caspase-3 and Bax gene protein expression levels was evaluated as indicator of apoptosis induction in treated- Hela cells. The antioxidant activity was evaluated using three methods,(DPPH, Reducing power and ABTS) andanti-inflammatory activity measured by two systems (in vivo and in vitro). The obtained results showed that all studied extracts expressed significant in vitro cytotoxic activity toward HeLa, and EACC cell lines. The data revealed up regulation of both Bax and caspase-3 protein expressions levels in treated-HeLa cell line. In DPPH assay aqueous MeOH extracts of Gelidium pulchrum exhibit maximum inhibition (IC50= 51±2.3). The highest reducing power was 179.3±4.7µg/mL GAE in aqueous MeOH extract of Gelidium pulchrum. The data also showed that all tested extracts have anti-nflammatory activity against carrgeenan induced paw oedema. While absolute MeOH extract of Gelidium pulchrum has maximum protection (71.7±1.7 %) in membrane stabilization test. Data obtained indicate the potential of these algal extracts for the antitumor through induction of apoptosis in cancer cells in addition to, the antioxidant and anti-inflammatory actions. This biological action is interesting for further isolation and identification of new natural anticancer and antioxidant compounds.
References
. Cardozo KH, Guaratini T, Barros MP, Falcão VR, Tonon AP, Lopes NP, Campos S, Torres MA, Souza AO, Colepicolo P and Pinto E, Metabolites from algae with economical impact, Comp Bioch and Phys., 2007; 146 (1-2) : 60–78 .
. Mayer A and Lehmann V, Marine pharmacology in: antitumor and cytotoxic compounds. Anticer Res., 2001; 21:2489–2500.
. Mayer AM and Gustafson KR, Marine pharmacology in: antitumor and cytotoxic compounds. International Journal of Cancer, 2003; (105):291–299
. Faulkner DJ, Marine natural products. Nat Prod Rep., 2000;17:7–55
.Rinehart KL , Shaw PD, Shield LS, Gloer JB, Harbour GC, Koker MES, Samain D, Schwartz RE, Tymiak AA, Weller DL, Carter GT and Munro MH Marine natural products as sources of antiviral, antimicrobial, and antineoplastic agents. Pure and Appl Chem., 1981; 53:795–871
. Tziveleka LA, Vagias C and Roussis V , Natural products with anti-HIV activity from marine organisms. Cur Top in Med. Chem.,2003; 3(13):1512–35.
. Konig GM and Wright AD, Marine natural products research. Current directions and future potential. Plan Med, 1995; 62:193–11
. Bechelli J, Coppage M, Rosell K and Liesveld J , Cytotoxicity of algae extracts on normal and malignant cells. Leukemia Research Treatment, 2011; Article ID 373519, 7 pages .
. Li B, Chu X, Gao M, Li W , Apoptotic mechanism of MCF-7 breast cells in vivo and in vitro induced by photodynamic therapy with C phycocyanin. Acta Bioch et Biophy Sin., 2010; 42:80–9
. Oftedal L, Selheim F, Wahlsten M, Sivonen K, Døskeland SO and Herfindal L , Marine benthic cyanobacteria contain apoptosis-inducing activity synergizing with daunorubicin to kill leukemia cells, but not cardiomyocytes. Mar Drug.,2010; 8:2659–72.
. Shibata MA, Maroulakour IG, Jorcyk C L, Gold LG, Ward JM and Green JE , p53-dependent apoptosis during mammary tumor progression in C3(1)/SV40 large T antigen transgenic mice: suppression of apoptosis during the transition from preneoplasia to carcinoma. Can. Res.1996; 56 :2998 -03 .
. Das T , Sa G , Sinha P and Ray P K, Induction of cell proliferation and apoptosis: dependence on the dose of the inducer. Bioch and Biophy Res. Com.1999; 260,105–10.
. Basu A and Haldar S, The relationship between BcI2, Bax and p53: consequences for cell cycle progression and cell death. Mol Hum Rep.1998; 4: 1019-99 .
. Levin A, p53, the cellular gatekeeper for growth and division. Cell 1997; 88 : 323-31
. Miyashita T and Reed JC, Tumor suppressor p53 is a direct transcriptional activator of the human Bax gene. Cell, 1997; 80: 293–99 .
. Miyashita T, Krajewski S , Krajewska M , Wang HG, Lin HK , Liebermann DA, Hoffman B and Reed JC,( 1994) Tumor suppressor p53 is a regulator of Bcl-2 and Bax gene expressionin vitro and in vivo. Onco.,1994; 9: 799–05.
. Miller TM, Moulder KL, Knudson CM, Creedon DJ, Deshmukh M, Korsmeyer SJ and Johnson EM, Bax deletion further orders the cell death pathway in cerebellar granule cells and suggests a caspase independent pathway to cell death. J of Cell Bio. 1997; 139:205–17 .
. Martinou I, Missotten M, Fernandez PA, Sadoul R and Martinou JC, Bax and Bak proteins require caspase activity to trigger apoptosis in sympathetic neurons. Neur. 1998; 9:15–9 .
Thornberry NA and Lazebnik Y, Caspases: enemies within. Sci.,1998; 281:1312–16 .
. Singleton V, Orthofer R and Lamuela-Ravento R, Analysis of total phenols and other oxidation substrates and antioxidants by means of Folin- Ciocalteu reagent. InL.Packer (Ed.). Oxidants and antioxidants, part A, Methods in enzymology,1999; 299: 152-78. New York: Academic Press .
. Matyuschenko N and Stepanova T , Quantitative determination of total content of flavonoids in the new phytopreparation Elima. Pharm. Chem. 2003; 37:261-263.
. Bennett JM, Catovsky D, Danniel MT, Galton DG, Graanlnik HR and Sultan C, Proposal for the classification of the acute leukemia. Brit J of Heam . 1976., 33: 451-8
. Denizot F and Lang R,. Rapid colorimetric assay for cell growth and survival. Modifications to the tetrazolium dye procedure giving improved sensitivity and reliability. J of Imm.Meth., 1986; 89:1-7.
. Thirumal M, Vadivelan R, Kishore G and Brahmaji VS, Aristolochia bracteolata: An Overview on Pharmacognostical, Phytochemical and Pharmacological roperties. Crit Rev Pharm Sci, 2012; 1: 66-78 .
Blois MS, Antioxidant determinations by the use of a stable free radical. Nat.1958; 26: 1199-1200 .
. Dorman H, Kosar M, Kahlos K, Holm Y and Hiltunen R, Antioxidant properties and composition of aqueous extracts from Mentha species, hybrids, varieties, and cultivars. J Agri and Food Chem., 2003; 51: 4563-4569 .
. Re R , Pellegrini N, Proteggente A, Pannala, A, Yang M, and Rice-Evans C, Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Rad Bio and Med., 1999; 26(9–10): 1231–37.
. Winter CA, Risley EA and Nuss GW, Carrageenin-induced edema in hind paw of the rat as an assay for anti-inflammatory drugs. Proceedings of the Soci.for Experi Bio and Med, 1962; 111: 544-7
. Gandhidasan R, Thamaraichelvan A and Baburaj S, Anti inflammatory action of Lannea coromandelicaby HRBC membrane stabilization. Fito.1991; 62: 81-3.
. Vinson JA, Yong H, Xuchui S and Zubik L , Phenol antioxidant quantity and quality in foods: vegetables. J. Agri Food Chem.,1998; 46: 3630-34.
.Okawa M, Kinjo J, Nohara T, Ono M , DPPH (1,1-diphenyl-2 picrylhydrazyl) radical scavenging activity of flavonoids obtained from some medicinal plants. Bio & Pharm Bull.,2001; 24:1202–1205.
. Arora A, Nair MG and Strasburg GM, Structure-activity relationships for antioxidant activities of a series of flavonoids in a liposomal system. Free Rad Bio and Med., 1998; 24:1355-63.
Faulkner DJ, Marine natural products. Nat Prod Rep., 2002; 19(1):1–48 .
. Liu M, Hansen PE and Lin X, Bromophenols in marine algae and their bioactivities. Mar Dr, 2011; 9(7):1273–92 .
. DeFilippis RA, Goodwin EC, Wu L and DiMaio D, Endogenous human
papillomavirus E6 and E7 proteins differentially regulate proliferation, senescence and apoptosis in HeLa cervical carcinoma cells. J of Vir., 2003; 77:1551–1563.
. Pang M, Gao Wu Z, Lv N, Wang Z, Tang X and Qu P, Apoptosis induced by
yessotoxins in HeLa human cervical cancer cells in vitro.. Mol Med Rep.,2010;, 3:629–34 .
. Misurcova L, Skrovankova S, Samek D, Ambrozova J and Machu L, Healthbenefits of algal polysaccharides in human nutrition. Adv in Food and Nutr Res.,2010; 66:75–145 .
. Zandi K, Tajbakhsh S, Nabipour I, Rastian Z, Yousefi F, Sharafian S and Sartavi K, In vitro antitumor activity of Gracilaria corticata (a red alga) against Jurkat and molt-4 human cancer cell lines. Afri J of Biotech., 2007; 9(40):6787–90 .
Yeh CC, Tseng CN, Yang JI, Huang HW, Fang Y, Tang JY, Chang FR and Chang HW. Antiproliferation and induction of apoptosis in Ca9-22 oral cancer cells byethanolic extract of Gracilaria tenuistipitata. Mol.,2012a; 17(9):10916–27 .
. Yeh CC, Yang JI, Lee JC, Tseng CN, Chan YC, Hseu YC, Tang JY, Chuang LY,Huang HW, Chang FR, Anti-proliferative effect of methanolic extract of Gracilaria tenuistipitataon oral cancer cells involves apoptosis, DNA damage, and oxidative stress. BMC Compl and Alter Med., 2012b; 12(1):142 .
.Paul S and Kundu R , Antiproliferative activity of methanolic extracts from two green algae, Enteromorpha intestinalis and Rizoclonium ripariumon on HeLa cells DARU J of Pharm Sci., 2013; 21:72 .
. Kim JY, Yoon MY, Cha MR, Hwang JH, Park E, Choi SU, Park HR and Hwang YI ,Methanolic extracts of Plocamium telfairiae induce cytotoxicity and caspase-dependent apoptosis in HT-29 human colon carcinoma cells. J Med Food, 2007; 10(4):587–593 .
. Park HY, Lim CW, Kim YK, Yoon HD and Lee KJ, Immunostimulating and anticancer activities of hot water extract from Capsosiphon fulvescens. J of the Kor Soc for Appl Biol Chem, 2006; 49.:343–348 .
. Nakajima K, Yokoyama A and Nakajima Y, Anticancer effects of a tertiary
sulfonium compound, dimethylsulfoniopropionate, in green sea algae on Ehrlich ascites carcinoma-bearing mice. J of nutr sci and vit., 2009; 55(5):434–438
.Bhattacharyya, A Choudhuri, T Pal S, Chattopadhyay S , Datta, G Sa g and Das T , Apoptogenic effects of black tea on Ehrlich’s ascites carcinoma cell Carc.,2003; 24 (1) : 75–80 .
. Li Y and Zhang X. Recombinant Microcystis viridis lectin as a potential anticancer agent.Pharm., 2010; 65(12):922–923 .
. Kelman D, Posner EK, McDermid KJ, Tabandera NK, Wright PR and Wright AD, Antioxidant activity of Hawaiian marine algae. Mar Dru., 2012; 10(2):403–416 .
Heo SJ, Jeon YJ, Lee J, Kim HT and Lee KW, Antioxidant effect of enzymatic hydrolyzate from a Kelp. Ecklonia cava. Alg., 2003a18(4):341–347 .
. Heo SJ, Lee KW, Song CB and Jeon YJ , Antioxidant activity of enzymatic extracts from brown seaweeds.Alg,2003b; 18:71–81 .
. Plaza, M. Cifuentes, A and Ibanez, E , “In the search of new functional food ingredients from algae,” Trends in Food Sci and Tech.,2008; 19(1) : 31–9
. Shanab S, Shalaby, E and El-Fayoumy E , Enteromorpha compressa Exhibits Potent Antioxidant Activity. Journal of Biomedicine and Biotechnology Vol 2011, Article ID 726405,11 pages doi:10.1155/2011/726405
. Farasat M, Khavari-Nejad R , Nabavi S , Namjooyan F , Antioxidant Properties of two Edible Green Seaweeds From Northern Coasts of the Persian Gulf Jundishapur J of Nat.Pharm Prod., 2013; 8(1) : 47-52 .
. Benzie IFF, and Strain JJ, The ferric reducing ability of plasma (FRAP) as a measure of ‘‘antioxidant power”: The FRAP assay. Anal Bioch., 1996; 239: 70-6 .
. Abou Elella F and. Shalaby E , Antioxidant activity of extract and semi- purified fractions of marine red macroalga,gracilaria verrucosa Aust. J. Basic and Appl Sci.,2009; 3(4): 3179-85
. Gavamukulya Y , Abou-Elella F , Wamunyokoli F and El-Shemy H, Phytochemical screening, anti-oxidant activity and in vitro anticancer potential of ethanolic and water leaves extracts of Annona muricata (Graviola) Asia Pac J Trop Biomed., 2014; 4(1):930-39 .
. Ialenti A, Ianaro A, Moncada S and Di Rosa M, Modulation of acute inflammation by endogenous nitric oxide. Eur Jof Pharm., 1995; 211: 177-182.
. Heller A, Koch T, Schmeck J and Ackern KV , Lipid mediators in inflammatory disorders. Drug.,1998; 554: 487–96 .
. Salvemini D, Wang Z Q and Wyatt P S, “Nitric oxide: a key mediator in the early and late phase of carrageenan-induced rat paw inflammation,” Bri J of Pharm., 1996; 118: (4 ) 829–838.
. Rang HP, Dale, MM, Ritter, JM, Flower RJ and. Henderson G , Pharmacology, Elsevier Churchill Livingstone, Edinburgh, UK, 7th edition (2011).
. Liu M, Hansen PE, Lin X, Bromophenols in marine algae and their bioactivities. Mar Dru., 2011; 9(7):1273–1292 .
. Kim SK and Ta QV, Potential beneficial effects of marine algal sterols on human health. Adv Food Nutr Res, 2011; 64:191–8
. Fedorov S, Ermakova S , Zvyagintseva T and Stonik V, Anticancer and Cancer Preventive Properties of Marine Polysaccharides: Some Results and Prospects Mar Dru,2013; 11, 4876-4901
. Jimenez-Escrig A, Gomez-Ordonez E and Ruperez P, Seaweed as a source of novel nutraceuticals: sulfated polysaccharides and peptides. Adv.in Food and Nut Res., 2011; 64:325–337 .
. Kim SK and Li YX, Medicinal benefits of sulfated polysaccharides from sea vegetables. Adv in Food and Nutr Res., 2011; 64:391–402 .
. Murugasan N,Vember S and Damodharan C, Studies on erythrocyte membrane IV, in vitro hemolytic activity of olender extract, Tox, Lett, 1981; 8: 33-8 .
. Chou CT, The anti-inflammatory effect of Tripterygium wilfordii Hook F on adjuvant induced paw edema in rats and inflammatory mediators’ release. Phyto Res., 1997; 11: 152-154 .
. Tabarsa M, Rezaei M, Ramezanpour Z and Waaland JR , Chemical compositions of the marine algae Gracilaria salicornia (Rhodophyta) and Ulva lactuca (Chlorophyta) as a potential food source. Journal of the Science of Food and Agriculture, 92(12):2500–2506 (2012).
. Rajapakse N and Kim SK , Nutritional and digestive health benefits of seaweed. Adv in Food and Nutr Res., 2011; 64:17- 28 .
. Souza BW, Cerqueira MA, Martins JT, Quintas MA, Ferreira AC, Teixeira JA and Vicente AA , Antioxidant potential of two red seaweeds from the Brazilian coasts. J of Agri and Food Chem., 2011; 59(10):5589–5594 .
. Yeh ST, Lin YC, Huang CL, Chen JC. White shrimp Litopenaeus vannamei that received the hot-water extract of Gracilaria tenuistipitata showed protective innate immunity and up-regulation of gene expressions after low-salinity stress. Fish Shellfish Imm., 2010; 28(5–6):887–894 .
. Coura CO, de Araujo IW, Vanderlei ES, Rodrigues JA, Quindere AL, Fontes BP, de Queiroz IN, de Menezes DB, Bezerra MM, and Silva AA, Antinociceptive and anti-inflammatory activities of sulphated polysaccharides from the red seaweed Gracilaria cornea. Bas & Clin Pharm & Toxi., 2012; 110(4):335–341 .
. Genovese G, Tedone L, Hamann MT and Morabito M, The Mediterranean redalga Asparagopsis: a source of compounds against Leishmania.Mar species and risk of atherosclerosis. Current Atherosclerosis Reports, 14(3):264–276 (2012).
.Lavanya R , Uma MaheshwarG, Harish,J, Bharath Raj, S Kamal, D , Hemamalani J, Bharathvarma C and Umamaheswara Reddy, investigation of in vitro anti inflammatory, anti platelet and and arthritic activities in the leaves of Anisomeles malabarica L, Res J of Pharm, Bio and Chem Sci., 2010; 1(4)745-752 .
. Manjunatha B.K Murthuza S, Divakara R, Antioxidant and Anti-Inflammatory Potency of Mesua Ferrea Linn Ind J of Appl Res., 2013; 3(8) 55-58 .
. Wang W, Wang SX and Guan HS. The antiviral activities and mechanisms of marine polysaccharides: an overview. Mar Drug, 2012; 10(12):2795–2816.
. D’Orazio N, Gammone MA, Gemello E, De Girolamo M, Cusenza S, Riccioni G, Marine bioactives: pharmacological properties and potential applications against inflammatory diseases. Mar Drug., 2012; 10(4):812–833.
