Nanoliposomal formulation of Agrostemma githago aqueous extract shows enhanced cytotoxic effect on gastric cancer cell line

Document Type: Research Paper

Authors

1 Department of Pharmacology, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran

2 Drug and Advanced Sciences Research Center, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran

10.7508/nmj.2015.01.002

Abstract

Objective(s):
The objective of this study was to determine the cytotoxic effects of nanoliposomal form of lyophilized aqueous extract of Agrostemma githago (A. githago) seeds on gastric cancer cell line (AGS) using cell viability tests.
Materials and Methods:
Lyophilized aqueous extract of A. githago seeds was prepared. Liposomes were also prepared by thin-film hydration method and their stability and size were characterized by SEM. The size and zeta potential were determined by Malvern Zetasizer. Cytotoxic effects of nanoliposomes on gastric cancer cell line was determined using MTT, Neutral Red and Frame methods.
Results:
The size of liposomes was around 171.5 nm with proper dispersion (PDI=0.268). The morphology of the liposomes was suitable according to SEM images. The IC50 values indicated that the nanoliposomal form of extract was 3-4 times more active than extract alone. Average IC50 values for extract and liposomal form of extract were 13.02 ± 0.95 and 4.43 ± 1.49 ug/ml, respectively.
Conclusion:
This study showed that liposomal form of aqueous extract of A. githago seeds exerts cytotoxic effect at significantly lower concentrations than the extract itself.

Keywords


  1. Koz O, Bedir E, Masullo M, Alankus-Caliskan O, Piacente S. Triterpene glycosides from Agrostemma gracilis. Phytochemistry. 2010;71(5-6): 663-668.
  2. Malcherek K, Breuer J, Schuphan I, Schmidt B. Metabolism of 4-nitrophenol in aseptically cultivated plants of the species wheat (Triticum aestivum L.), soybean (Glycine max L.), wild oat (Avena fatua L.) and corn cockle (Agrostemma githago L.). J Plant Physiol. 1998; 153(1-2): 192-199.
  3. Kollmann J, Bassin S. Effects of management on seed predation in wildflower strips in northern Switzerland. Agric Ecosyst Environ. 2001; 83(3): 285-296.
  4. Siepmann C, Bader G, Hiller K, Wray V, Domke T, Nimtz M. New saponins from the seeds of Agrostemma githago var. githago. Planta Medica. 1998; 64(2): 159-164.
  5. Hebestreit P, Melzig MF. Cytotoxic activity of the seeds from Agrostemma githago var. githago. Planta Medica. 2003; 69(10): 921-925.
  6. Heisler I, Sutherland M, Bachran C, Hebestreit P, Schnitger A, Melzig MF, et al. Combined application of saponin and chimeric toxins drastically enhances the targeted cytotoxicity on tumor cells. J Control Release. 2005; 106(1-2): 123-137.
  7. Hebestreit P, Weng A, Bachran C, Fuchs H, Melzig MF. Enhancement of cytotoxicity of lectins by Saponinum album. Toxicon. 2006; 47(3): 330-335.
  8. Ueda S, Nakamura H, Masutani H, Sasada T, Takabayashi A, Yamaoka Y, et al. Baicalin induces apoptosis via mitochondrial pathway as prooxidant. Mol Immunol. 2002; 38(10): 781-791.
  9. Heim KE, Tagliaferro AR, Bobilya DJ. Flavonoid antioxidants: chemistry, metabolism and structure-activity relationships. J Nutr Biochem. 2002; 13(10): 572-584.
  10. Ismail N, Alam M. A novel cytotoxic flavonoid glycoside from Physalis angulata. Fitoterapia. 2001; 72(6): 676-679.
  11. Hodek P, Trefil P, Stiborová M. Flavonoids-potent and versatile biologically active compounds interacting with cytochromes P450. Chem Biol Interact. 2002; 139(1): 1-21.
  12. Agati G, Azzarello E, Pollastri S, Tattini M. Flavonoids as antioxidants in plants: Location and functional significance. Plant Sci. 2012; 196: 67-76.
  13. Williams RJ, Spencer JPE, Rice-Evans C. Flavonoids: Antioxidants or signalling molecules? Free Radic Biol Med. 2004; 36(7): 838-849.
  14. Mozafari MR. Nanoliposomes: preparation and analysis. Methods Mol Biol. 2010; 605: 29-50.
  15. Sharma A, Sharma US. Liposomes in drug delivery: Progress and limitations. Int J Pharm. 1997; 154(2): 123-140.
  16. Gabizon AA. Liposome circulation time and tumor targeting: Implications for cancer chemotherapy. Adv Drug Deliver Rev. 1995; 16(2-3): 285-294.
  17. Sun NF, Meng QY, Tian AL, Hu SY, Wang RH, Liu ZX, et al. Nanoliposome-mediated FL/TRAIL double-gene therapy for colon cancer: In vitro and in vivo evaluation. Cancer Lett. 2012; 315(1): 69-77.
  18. Huang FYJ, Lee TW, Kao CHK, Chang CH, Zhang X, Lee WY, et al. Imaging, autoradiography, and biodistribution of 188Re-labeled PEGylated nanoliposome in orthotopic glioma bearing rat model. Cancer Biother Radiopharm. 2011; 26(6): 717-725.
  19. Zhang LJ, Xing B, Wu J, Xu B, Fang XL. Biodistribution in mice and severity of damage in rat lungs following pulmonary delivery of 9-nitrocamptothecin liposomes. Pulm Pharmacol Ther. 2008; 21(1): 239-246.
  20. Ma J, Guan R, Shen H, Lu F, Xiao C, Liu M, et al. Comparison of anticancer activity between lactoferrin nanoliposome and lactoferrin in Caco-2 cells in vitro. Food Chem Toxicol. 2013; 59: 72-77.
  21. Chen C, Han D, Cai C, Tang X. An overview of liposome lyophilization and its future potential. J Control Release. 2010; 142(3): 299-311.
  22. Bisht S, Feldmann G, Soni S, Ravi R, Karikar C, Maitra A. Polymeric nanoparticle-encapsulated curcumin ("nanocurcumin"): A novel strategy for human cancer therapy. J Nanobiotechnology. 2007; 5. doi:10.1186/1477-3155-5-3.
  23. Kong B, Zhang H, Xiong YL. Antioxidant activity of spice extracts in a liposome system and in cooked pork patties and the possible mode of action. Meat Sci. 2010; 85(4): 772-778.
  24. Basomba A, Tabar AI, De Rojas DHF, García BE, Alamar R, Olaguíbel JM, et al. Allergen vaccination with a liposome-encapsulated extract of Dermatophagoides pteronyssinus: A randomized, double-blind, placebo-controlled trial in asthmatic patients. J Allergy Clin Immunol. 2002; 109(6): 943-948.
  25. Avci G, Kupeli E, Eryavuz A, Yesilada E, Kucukkurt I. Antihypercholesterolaemic and antioxidant activity assessment of some plants used as remedy in Turkish folk medicine. J Ethnopharmacol. 2006; 107(3): 418-423.
  26. Yoshie M, Masayuki N, Tsuneji N. Surface potential of liposomes with entrapped insulin. Int J Pharm. 1990; 64(2-3): 89-98.
  27. Muramatsu K, Maitani Y, Machida Y, Nagai T. Effect of soybean-derived sterol and its glucoside mixtures on the stability of dipalmitoylphosphatidylcholine and dipalmitoylphosphatidylcholine/cholesterol liposomes. Int J Pharm. 1994; 107(1): 1-8.
  28. Park SN, Lee MH, Kim SJ, Yu ER. Preparation of quercetin and rutin-loaded ceramide liposomes and drug-releasing effect in liposome-in-hydrogel complex system. Biochem Biophys Res Commun. 2013; 435(3): 361-366.
  29. Kumaran A, Joel Karunakaran R. In vitro antioxidant activities of methanol extracts of five Phyllanthus species from India. LWT-Food Sci Technol. 2007; 40(2): 344-352.
  30.  
  31. Bohlooli S, Jafari N, Jahed S. Cytotoxic effect of freeze-dried extract of Ecballium elaterium fruit on gastric adenocarcinoma (AGS) and esophageal squamous cell carcinoma (KYSE30) cell lines. J Gastrointest Cancer. 2012; 43(4): 579-583.
  32. Jafari N, Bohlooli S, Mohammadi S, Mazani M. Cytotoxicity of methylsulfonylmethane on gastrointestinal (AGS, HepG2, and KEYSE-30) cancer cell lines. J Gastrointest Cancer. 2012; 43(3): 420-425.
  33. Chen Y, Wu Q, Zhang Z, Yuan L, Liu X, Zhou L. Preparation of curcumin-loaded liposomes and evaluation of their skin permeation and pharmacodynamics. Molecules. 2012; 17(5): 5972-5987.
  34. Sou K. Electrostatics of carboxylated anionic vesicles for improving entrapment capacity. Chem Phys Lipids. 2011; 164(3): 211-215.
  35. Vert M, Doi Y, Hellwich K-H, Hess M, Hodge P, Kubisa P, et al. Terminology for biorelated polymers and applications. Pure Appl Chem. 2012; 84(2): 377-410.
  36. Munin A, Edwards-Levy F. Encapsulation
    of natural polyphenolic compounds; a review. Pharmaceutics. 2011; 3(4): 793-829.
  37. M.A. L-D, Wagner H. Saponins. In: Rahman A-U-, editor. Studies in Natural Products Chemistry Series. Netherland: Elsevier; 2000. p. 633–687.
  38. Onoue S, Yamada S, Chan HK. Nanodrugs: pharmacokinetics and safety. Int J Nanomedicine. 2014; 9: 1025-1037.