Nanoencapsulation of Syzygium polycephalum Extract Using Folate Modified κ-Carrageenan as Vehicles for Pronounced Anticancer Activity

doi.org/10.26538/tjnpr/v4i11.17

Authors

  • Andika P. Wardana Department of Chemistry, Faculty of Science and Technology, Universitas Airlangga, Kampus C-UNAIR, Jl. Mulyorejo, Surabaya 60115, Surabaya, Indonesia
  • Nanik S. Aminah Department of Chemistry, Faculty of Science and Technology, Universitas Airlangga, Kampus C-UNAIR, Jl. Mulyorejo, Surabaya 60115, Surabaya, Indonesia
  • Mochamad Z. Fahmi Department of Chemistry, Faculty of Science and Technology, Universitas Airlangga, Kampus C-UNAIR, Jl. Mulyorejo, Surabaya 60115, Surabaya, Indonesia
  • Alfinda N. Kristanti Department of Chemistry, Faculty of Science and Technology, Universitas Airlangga, Kampus C-UNAIR, Jl. Mulyorejo, Surabaya 60115, Surabaya, Indonesia
  • Haninda I. Zahrah Faculty of Dental Medicine, Universitas Airlangga, Kampus A-UNAIR, Jl. Mayjen Prof. Dr. Moestopo 47, Surabaya 60131, Surabaya, Indonesia
  • Yoshiaki Takaya Department of Pharmacy, Meijo University, Nagoya, Japan
  • M. Iqbal Choudhary H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan

Keywords:

Syzygium polycephalum, Nanoencapsulation, Folate receptor, Drug delivery system, Anticancer

Abstract

S. polycephalum (Sp) is an important species of the genus Syzygium. 3,4,3'-tri-O-methyl ellagic acid obtained from Sp, has potential as a natural anticancer agent. The drawback of natural products as medicine is their non-specific effects and poor solubility, so a better drug delivery system is needed to overcome this challenge. This study utilizes κ-carrageenan and carrageenan folate (Cf) as the carrier matrix. Sp-CNPs and Sp-CfNPs can increase the anticancer activity of Sp extract. The addition of folate groups to carrageenan gave better results in delivering the Sp  extract drug on the HeLa cell line and T47D cell line. The free Sp extract was able to inhibit the
growth of HeLa cancer cells with EC50 114.19 ± 10.31 μg/mL, while both Sp-CNPS and SpCfNPs nanocapsules showed EC50 79.19 ± 13.96 μg/mL and EC50 48.77 ± 15.91 μg/mL. In T47D cells, the free Sp extract showed EC50 498.33 ± 110.72 μg/mL. Sp-CNP nanocapsules were able to increase the anticancer activity of free Sp extract with EC50 80.62 ± 12.59 μg/mL, whereas Sp-CfNP performed anticancer activity against T47D cells with EC50 48.52 ± 2.76 μg/mL. 

Author Biographies

Nanik S. Aminah, Department of Chemistry, Faculty of Science and Technology, Universitas Airlangga, Kampus C-UNAIR, Jl. Mulyorejo, Surabaya 60115, Surabaya, Indonesia

Biotechnology of Tropical Medicinal Plants Research Group, Universitas Airlangga, Surabaya 60115, Surabaya, Indonesia

Alfinda N. Kristanti, Department of Chemistry, Faculty of Science and Technology, Universitas Airlangga, Kampus C-UNAIR, Jl. Mulyorejo, Surabaya 60115, Surabaya, Indonesia

Biotechnology of Tropical Medicinal Plants Research Group, Universitas Airlangga, Surabaya 60115, Surabaya, Indonesia

References

Torre LA, Bray F, Siegel RL, FerlayJ, Lortet‐Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015; 65(2):87-108.

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, JemalA. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018; 68(6): 394-424.

Nussbaumer S, Bonnabry P, Veuthey JL, Fleury-Souverain S. Analysis of anticancer drugs: a review. Talanta. 2011; 85(5):2265-2289.

Hosseini A and Ghorbani A. Cancer therapy with phytochemicals: evidence from clinical studies. Avicenna J Phytomed. 2015; 5(2):84-97.

Greenwell M and Rahman P. Medicinal plants: their use in anticancer treatment. Int J Pharm Sci Res. 2015; 6(10): 4103-4112.

Cheung A, Bax HJ, Josephs DH, Ilieva KM, Pellizzari G, Opzoomer J, Bloomfield J, Fittall M, Grigoriadis A, Figini M. Targeting folate receptor alpha for cancer treatment. Oncotarget. 2016; 7(32):52553.

Zwicke GL, Ali Mansoori G, Jeffery CJ. Utilizing the folate receptor for active targeting of cancer nanotherapeutics. Nano Reviews. 2012; 3(1):18496.

Gupta A, Kaur CD, Saraf S. Targeting of herbal bioactives through folate receptors: a novel concept to enhance intracellular drug delivery in cancer therapy. J Recept Signal Transduct. 2017; 37(3):314-323.

Ledermann J, Canevari S, Thigpen T. Targeting the folate receptor: diagnostic and therapeutic approaches to personalize cancer treatments. Ann Oncol. 2015; 26(10):2034-2043.

Müller C and Schibli R .Folic acid conjugates for nuclear imaging of folate receptor–positive cancer. J Nucl Med. 2011; 52(1):1-4.

Khodavirdipour A, Zarean R, Safaralizadeh R. Evaluation of the Anti-cancer Effect of Syzygium cumini Ethanolic Extract on HT-29 Colorectal Cell Line. J Gastrointes Cancer 2020.

Kubatka P, Uramova S, Kello M, Kajo K, Kruzliak P, Mojzis J, Vybohova D, Adamkov M, Jasek K, Lasabova Z. Antineoplastic effects of clove buds (Syzygium aromaticum L.) in the model of breast carcinoma. J Cell Mol Med. 2017; 21(11): 2837-2851.

Memon AH, Ismail Z, Aisha AF, Al-Suede FSR, Hamil MSR, Hashim S, Saeed MAA, Laghari M, Majid A, Shah AM. Isolation, characterization, crystal structure elucidation, and anticancer study of dimethyl cardamonin, isolated from Syzygium campanulatum Korth. Evid Based Complement Alternat Med. 2014; 2014:1-11.

Thampi N and Shalini JV. Bio-prospecting the in-vitro antioxidant and anti-cancer activities of silver nanoparticles synthesized from the leaves of Syzygium samarangense. Int J Pharm Pharm Sci. 2015; 7(7):269-274.

Annadurai G, Masilla BRP, Jothiramshekar S, Palanisami E, Puthiyapurayil S, Parida AK. Antimicrobial, antioxidant, anticancer activities of Syzygium caryophyllatum (L.) Alston. Int J Green Pharm. 2012; 6(4):285-288.

Kiruthiga K, Saranya J, Eganathan P, Sujanapal P, Parida A. Chemical composition, antimicrobial, antioxidant and anticancer activity of leaves of Syzygium benthamianum (Wight ex Duthie) Gamble. JBAPN. 2011; 1(4):273-278.

Islam S, Nasrin S, Khan MA, Hossain AS, Islam F, Khandokhar P, Mollah MNH, Rashid M, Sadik G, Rahman MAA. Evaluation of antioxidant and anticancer properties of the seed extracts of Syzygium fruticosum Roxb. growing in Rajshahi, Bangladesh. BMC Compl Altern Med. 2013;

(142):1-10.

Komuraiah B, Chinde S, Kumar AN, Srinivas K, Venu C, Kumar JK, Sastry K, Grover P. Isolation of phytochemicals from anticancer active extracts of Syzygium alternifolium Walp. leaf. Pharmacogn J. 2014; 6(4):83-85.

Tukiran T, Wardana AP, Hidayati N, Shimizu K. An Ellagic Acid Derivative and Its Antioxidant Activity of Stem Bark Extracts of Syzygium polycephalum Miq.(Myrtaceae). Indones J Chem. 2018; 18(1):26-34.

Wang N, Wang Q, Tang H, Zhang F, Zheng Y, Wang S, Zhang J, Wang Z, Xie X. Direct inhibition of ACTN4 by ellagic acid limits breast cancer metastasis via regulation of β-catenin stabilization in cancer stem cells. J Exp Clin Cancer Res. 2017; 36(1):172.

Xu W, Xu J, Wang T, Liu W, Wei H, Yang X, Yan W, Zhou W, Xiao J. Ellagic acid and Sennoside B inhibit osteosarcoma cell migration, invasion and growth by repressing the expression of c‑Jun. Oncol Lett. 2018; 16 (1):898-904.

Cheng H Lu C, Tang R, Pan Y, Bao S, Qiu Y, Xie M. Ellagic acid inhibits the proliferation of human pancreatic carcinoma PANC-1 cells in vitro and in vivo. Oncotarget 2017; 8(7):12301.

Liu H, Zeng Z, Wang S, Li T, Mastriani E, Li QH, Bao HX, Zhou YJ, Wang X, Liu Y. Main components of pomegranate, ellagic acid and luteolin, inhibit metastasis of ovarian cancer by down-regulating MMP2 and MMP9. Cancer Biol Ther. 2017; 18(12):990-999.

Huang ST, Wang CY, Yang RC, Chu CJ, Wu HT, Pang JH S. Phyllanthus urinaria increases apoptosis and reduces telomerase activity in human nasopharyngeal carcinoma cells. Complement Med Res. 2009; 16(1):34-40.

Mishra S and Vinayak M. Ellagic acid inhibits PKC signaling by improving antioxidant defense system in murine T cell lymphoma. Mol Biol Rep. 2014; 41(7):4187- 4197.

Eskandari E, Heidarian E, Amini S, Saffari-Chaleshtori J. Evaluating the effects of ellagic acid on pSTAT3, pAKT, and pERK1/2 signaling pathways in prostate cancer PC3 cells. J Cancer Res Ther. 2016; 12(4):1266-1271.

Mirsane S. Benefits of ellagic acid from grapes and pomegranates against colorectal cancer. Caspian J Intern Med. 2017; 8(3):226-227.

Bisen P, Bundela S, Sharma A. Ellagic acidchemopreventive role in oral cancer. J Cancer Sci Ther. 2012; 4(2):23-30.

Zhang H, Guo ZJ, Xu WM, You ZJ, Han L, Han YX, Dai LJ. Antitumor effect and mechanism of an ellagic acid derivative on the HepG2 human hepatocellular carcinoma cell line. Oncol Lett. 2014; 7(2):525-530.

de Molina AR, Vargas T, Molina S, Sánchez J, MartínezRomero J, González-Vallinas M, Martín-Hernández R, Sánchez-Martínez R, de Cedrón MG, Dávalos A. The ellagic acid derivative 4, 4′-di-O-methylellagic acid efficiently inhibits colon cancer cell growth through a mechanism involving WNT16. J Pharmacol Exp Ther. 2015; 353(2):433-444.

Alfei S, Turrini F, Catena S, Zunin P, Parodi B, Zuccari G, Pittaluga AM, Boggia R. Preparation of ellagic acid micro and nano formulations with amazingly increased water solubility by its entrapment in pectin or non-PAMAM dendrimers suitable for clinical applications. New J hem.

; 43(6):2438-2448.

Neamatallah T, El-Shitany N, Abbas A, Eid BG, Harakeh S, Ali S, Mousa S. Nano Ellagic Acid Counteracts CisplatinInduced Upregulation in OAT1 and OAT3: A Possible Nephroprotection Mechanism. Molecules. 2020; 25(13):3031

El-Shitany NA, Abbas AT, Ali SS, Eid B, Harakeh S, Neamatallah T, Al-Abd A, Mousa S. Nanoparticles Ellagic Acid Protects Against Cisplatin-induced Hepatotoxicity in Rats Without Inhibiting its Cytotoxic Activity. Int J Pharmacol. 2019; 15(4):465-477.

Badawi NM, Teaima MH, El-Say KM, Attia DA, ElNabarawi MA, Elmazar MM. Pomegranate extract-loaded solid lipid nanoparticles: design, optimization, and in vitro cytotoxicity study. Int J Nanomedicine. 2018; 13:1313.

Yao H, Liu J, Xu S, Zhu Z, Xu J. The structural modification of natural products for novel drug discovery. Expert Opin Drug Discov. 2017; 12(2):121-140.

Bharali DJ and Mousa SA. Emerging nanomedicines for early cancer detection and improved treatment: current perspective and future promise. Pharmacol Ther. 2010; 128(2):324-335.

Mehrnia MA, Jafari SM, Makhmal-Zadeh BS, Maghsoudlou Y. Crocin loaded nano-emulsions: factors affecting emulsion properties in spontaneous emulsification. Int J Biol Macromol. 2016; 84:261-267.

Fahmi MZ, Haris A, Permana AJ, Wibowo DLN, Purwanto B, Nikmah YL, Idris A. Bamboo leaf-based carbon dots for efficient tumor imaging and therapy. RSC Adv. 2018; 8(67): 38376-38383.

Gao X, Wu J, Zou W, Dai Y. Two ellagic acids isolated from roots of Sanguisorba officinalis L. promote hematopoietic progenitor cell proliferation and megakaryocyte differentiation. Molecules 2014; 19(4):5448-5458.

Tsakos M, Schaffert ES, Clement LL, Villadsen NL, Poulsen TB. Ester coupling reactions–an enduring challenge in the chemical synthesis of bioactive natural products. Nat Prod Rep. 2015; 32(4):605-632.

Mangione M, Giacomazza D, Bulone D, Martorana V, San Biagio P. Thermoreversible gelation of κ-Carrageenan: relation between conformational transition and aggregation. Biophysl Chem. 2003; 104(1):95-105.

Towle GA. Carrageenan. In Industrial gums, Elsevier: 1973; pp 83-114.

Danaei M, Dehghankhold M, Ataei S, Hasanzadeh Davarani F, Javanmard R, Dokhani A, Khorasani S, Mozafari M. Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics 2018; 10(2):1-17.

Worldwide MI. Dynamic light scattering, Common terms defined. Inform white paper. Malwern Instruments Limited. 2011; 2011:1-6.

Rizvi SA, Saleh AM. Applications of nanoparticle systems in drug delivery technology. Saudi Pharmaceutical Journal2018; 26(1):64-70.

Buzea C, Pacheco II, Robbie K. Nanomaterials and nanoparticles: sources and toxicity. Biointerphases. 2007; 2 (4):MR17-MR71.

Stanley N. Production, properties and uses of carrageenan. Production and utilization of products from commercial seaweeds. FAO Fisheries Technical Paper. 1987; 288:116- 146.

Capron I, Yvon M, Muller G. In-vitro gastric stability of carrageenan. Food hydrocolloids. 1996; 10(2):239-244.

Redhead H, Davis S, Illum L. Drug delivery in poly (lactide-co-glycolide) nanoparticles surface modified with poloxamer 407 and poloxamine 908: in vitro characterisation and in vivo evaluation. J Control Release. 2001; 70(3):353-363.

Parker N, Turk MJ, Westrick E, Lewis JD, Low PS, Leamon CP. Folate receptor expression in carcinomas and normal tissues determined by a quantitative radioligand binding assay. Anal Biochem. 2005; 338(2):284-293.

Fernández M, Javaid F, Chudasama V. Advances in targeting the folate receptor in the treatment/imaging of cancers. Chem Sci. 2018; 9(4):790-810.

Low PS and Kularatne SA. Folate-targeted therapeutic and imaging agents for cancer. Curr Opin Chem Biol. 2009; 13 (3):256-262.

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Published

2020-11-01

How to Cite

Wardana, A. P., Aminah, N. S., Fahmi, M. Z., Kristanti, A. N., Zahrah, H. I., Takaya, Y., & Choudhary, M. I. (2020). Nanoencapsulation of Syzygium polycephalum Extract Using Folate Modified κ-Carrageenan as Vehicles for Pronounced Anticancer Activity: doi.org/10.26538/tjnpr/v4i11.17. Tropical Journal of Natural Product Research (TJNPR), 4(11), 945–952. Retrieved from https://tjnpr.org/index.php/home/article/view/961