Comparison Between β-Cyclodextrin-Amygdalin Nanoparticle and Amygdalin Effects on Migration and Apoptosis of MCF-7 Breast Cancer Cell Line


Amygdalin is an herbal cyanoglycoside that has an anti-tumor effect. The utilization of this compound encounters various challenges results from releasing hydrogen cyanide. Apparently, the nano-formulation approach can increase its therapeutic effects. The β-cyclodextrin (β-CD) as a cyclic oligosaccharide is widely used in drug delivery. In this study, we aimed to nano-formulate the amygdalin by β-cyclodextrin in order to increase its effect on MCF-7 cell line. The synthesized β-CD-Amygdalin nanoparticle size, surface morphology, and chemical structure were determined by dynamic light scattering (DLS), Scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FT-IR), respectively. Also, we calculated the drug loading (DL), entrapment efficiency (EE), and drug releases. The MTT assay, wound-healing assay, real-time PCR, and flow cytometry assays were carried out to evaluate the β-CD-Amygdalin and amygdalin effects on cell viability, migration, expression of migration-related genes, and apoptosis, respectively. The results showed that the nanoparticle synthesized in the mean diameter of 54.94 nm with − 27.9 mV zeta potential, uniformity of shape, and expected structure. The DL and EE values were calculated in 17.5% and 90%. A slow curve of the amygdalin release profile with two burst release times in 6 h and 48 h was observed. The cellular and molecular evaluation of β-CD-Amygdalin and amygdalin effects on MCF-7 cells revealed that the β-CD-Amygdalin had greater effects than amygdalin. In conclusion, these results suggest that the nanoformulation of amygdalin with β-CD may elevate amygdalin therapeutic efficacy.

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  1. 1.

    P. Liczbinski and B. Bukowska (2018). Molecular mechanism of amygdalin action in vitro: review of the latest research. Immunopharmacol. Immunotoxicol. 40 (3), 212–218.

    CAS  Article  PubMed  Google Scholar 

  2. 2.

    Z. Zdrojewicz, A. Otlewska, P. Hackemer, and A. Otlewska (2015). Amygdalin—structure and clinical significance. Polski merkuriusz lekarski 38 (227), 300–303.

    PubMed  Google Scholar 

  3. 3.

    V. Jaswal, J. Palanivelu, and C. Ramalingam (2018). Effects of the Gut microbiota on Amygdalin and its use as an anti-cancer therapy: Substantial review on the key components involved in altering dose efficacy and toxicity. Biochem. Biophys. Rep. 14, 125–132.

    Article  PubMed  PubMed Central  Google Scholar 

  4. 4.

    S. Xu, X. Xu, S. Yuan, H. Liu, M. Liu, Y. Zhang, H. Zhang, Y. Gao, R. Lin, and X. Li (2017). Identification and analysis of amygdalin, neoamygdalin and amygdalin amide in different processed bitter almonds by HPLC-ESI-MS/MS and HPLC-DAD. Molecules 22 (9), 1425.

    CAS  Article  PubMed Central  Google Scholar 

  5. 5.

    M. F. Wahab, Z. S. Breitbach, D. W. Armstrong, R. Strattan, and A. Berthod (2015). Problems and pitfalls in the analysis of amygdalin and its epimer. J. Agric. Food Chem. 63 (40), 8966–8973.

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    B. Mosayyebi, M. Imani, L. Mohammadi, A. Akbarzadeh, N. Zarghami, M. Edalati, E. Alizadeh, and M. Rahmati (2020). An update on the toxicity of cyanogenic glycosides bioactive compounds: possible clinical application in targeted cancer therapy. Mater. Chem. Phys. 246, 122841.

    CAS  Article  Google Scholar 

  7. 7.

    H. Sauer, C. Wollny, I. Oster, E. Tutdibi, L. Gortner, S. Gottschling, and S. Meyer (2015). Severe cyanide poisoning from an alternative medicine treatment with amygdalin and apricot kernels in a 4-year-old child. Wiener medizinische Wochenschrift 165 (9–10), 185–188.

    Article  PubMed  Google Scholar 

  8. 8.

    T. Dang, C. Nguyen, and P. N. Tran (2017). Physician beware: severe cyanide toxicity from amygdalin tablets ingestion. Case Rep. Emerg. Med. 35, 4289527.

    Article  Google Scholar 

  9. 9.

    C. G. Moertel, M. M. Ames, J. S. Kovach, T. P. Moyer, J. R. Rubin, and J. H. Tinker (1981). A pharmacologic and toxicological study of amygdalin. Jama 245 (6), 591–594.

    CAS  Article  Google Scholar 

  10. 10.

    X. Y. He, L. J. Wu, W. X. Wang, P. J. Xie, Y. H. Chen, and F. Wang (2020). Amygdalin—a pharmacological and toxicological review. J. Ethnopharmacol. 254, 112717.

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    C. C. Bai, B. R. Tian, T. Zhao, Q. Huang, and Z. Z. Wang (2017). Cyclodextrin-catalyzed organic synthesis: reactions, mechanisms, and applications. Molecules 22 (9), 1475.

    CAS  Article  PubMed Central  Google Scholar 

  12. 12.

    H. Leemhuis, R. M. Kelly, and L. Dijkhuizen (2010). Engineering of cyclodextrin glucanotransferases and the impact for biotechnological applications. Appl. Microbiol. Biotechnol. 85 (4), 823–835.

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    F. Topuz and T. Uyar (2018). Electrospinning of cyclodextrin functional nanofibers for drug delivery applications. Pharmaceutics 11 (1), 6.

    CAS  Article  PubMed Central  Google Scholar 

  14. 14.

    B. Gidwani and A. Vyas (2015). A Comprehensive review on cyclodextrin-based carriers for delivery of chemotherapeutic cytotoxic anticancer drugs. Biomed. Res. Int. 21, 198268–198268.

    CAS  Article  Google Scholar 

  15. 15.

    A. J. S. P. Rasheed (2008). Cyclodextrins as drug carrier molecule: a review. Sci. Pharm. 76 (4), 567–598.

    CAS  Article  Google Scholar 

  16. 16.

    E. Abbasi, A. Akbarzadeh, M. Kouhi, and M. Milani (2016). Graphene: synthesis, bio-applications, and properties. Artif. Cells Nanomed. Biotechnol. 44 (1), 150–156.

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    F. Ahmadi-Aghkand, S. Gholizadeh-Ghaleh Aziz, Y. Panahi, H. Daraee, F. Gorjikhah, S. Gholizadeh-Ghaleh Aziz, A. Hsanzadeh, and A. J. A. C. Akbarzadeh (2016). Biotechnology recent prospective of nanofiber scaffolds fabrication approaches for skin regeneration. Nanomedicine 44 (7), 1635–1641.

    CAS  Google Scholar 

  18. 18.

    M. Saleem, J. Asif, M. Asif, and U. Saleem (2018). Amygdalin from apricot kernels induces apoptosis and causes cell cycle arrest in cancer cells: an updated review. Anti-Cancer Agents Med. Chem. 18 (12), 1650–1655.

    CAS  Article  Google Scholar 

  19. 19.

    J. Shi, Q. Chen, M. Xu, Q. Xia, T. Zheng, J. Teng, M. Li, and L. Fan (2019). Recent updates and future perspectives about amygdalin as a potential anticancer agent: a review. Cancer Med. 8 (6), 3004–3011.

    Article  PubMed  PubMed Central  Google Scholar 

  20. 20.

    T. Dang, C. Nguyen, and P. N. Tran (2017). Physician beware: severe cyanide toxicity from amygdalin tablets ingestion. Case Rep. Emerg. Med. 2017, 4289527–4289527.

    Article  PubMed  PubMed Central  Google Scholar 

  21. 21.

    J. Bromley, B. G. Hughes, D. C. Leong, and N. A. Buckley (2005). Life-threatening interaction between complementary medicines: cyanide toxicity following ingestion of amygdalin and vitamin C. Ann. Pharmacother. 39 (9), 1566–1569.

    Article  PubMed  Google Scholar 

  22. 22.

    A. Kumar and C. K. Dixit, 3—Methods for characterization of nanoparticles, in S. Nimesh, R. Chandra, and N. Gupta (eds.), Advances in nanomedicine for the delivery of therapeutic nucleic acids (Woodhead Publishing, Cambridge, 2017), pp. 43–58.

    Google Scholar 

  23. 23.

    K. P. Sambasevam, S. Mohamad, N. M. Sarih, and N. A. Ismail (2013). Synthesis and characterization of the inclusion complex of β-cyclodextrin and azomethine. Int. J. Mol. Sci. 14 (2), 3671–3682.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  24. 24.

    V. Webber, D. de Siqueira Ferreira, P. L. M. Barreto, V. Weiss-Angeli, and R. Vanderlinde (2018). Preparation and characterization of microparticles of β-cyclodextrin/glutathione and chitosan/glutathione obtained by spray-drying. Food Res. Int. (Ottawa, Ont) 105, 432–439.

    CAS  Article  Google Scholar 

  25. 25.

    I. M. Savic, V. D. Nikolic, I. M. Savic-Gajic, L. B. Nikolic, S. R. Ibric, and D. G. Gajic (2015). Optimization of technological procedure for amygdalin isolation from plum seeds (Pruni domesticae semen). Front. Plant Sci. 6, 276.

    Article  PubMed  PubMed Central  Google Scholar 

  26. 26.

    A. Hedges, Chapter 22—cyclodextrins: properties and applications, in J. BeMiller and R. Whistler (eds.), Starch, 3rd ed. (Academic Press, San Diego, 2009), pp. 833–851.

    Google Scholar 

  27. 27.

    M. J. Vazquez-Mellado, V. Monjaras-Embriz, and L. Rocha-Zavaleta, Chapter fourteen—erythropoietin, stem cell factor, and cancer cell migration, in G. Litwack (ed.), Vitamins and hormones, vol. 105 (Academic Press, New York, 2017), pp. 273–296.

    Google Scholar 

  28. 28.

    S. Kurosaka and A. Kashina (2008). Cell biology of embryonic migration. Birth Defects Res C Embryo Today 84 (2), 102–122.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  29. 29.

    L. Li, Y. He, M. Zhao, and J. Jiang (2013). Collective cell migration: implications for wound healing and cancer invasion. Burns Trauma 1 (1), 21–26.

    Article  PubMed  Google Scholar 

  30. 30.

    J. Mani, J. Neuschäfer, C. Resch, J. Rutz, S. Maxeiner, F. Roos, F. K. Chun, E. Juengel, and R. A. Blaheta (2020). Amygdalin modulates prostate cancer cell adhesion and migration in vitro. Nutr. Cancer 72 (3), 528–537.

    CAS  Article  PubMed  Google Scholar 

  31. 31.

    J. Makarević, J. Rutz, E. Juengel, S. Kaulfuss, I. Tsaur, K. Nelson, J. Pfitzenmaier, A. Haferkamp, and R. A. Blaheta (2014). Amygdalin influences bladder cancer cell adhesion and invasion in vitro. PLoS ONE 9 (10), e110244–e110244.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  32. 32.

    J.-L. Maître and C.-P. Heisenberg (2013). Three functions of cadherins in cell adhesion. Curr. Biol. 23 (14), R626–R633.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  33. 33.

    A. Jeanes, C. J. Gottardi, and A. S. Yap (2008). Cadherins and cancer: how does cadherin dysfunction promote tumor progression? Oncogene 27 (55), 6920–6929.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  34. 34.

    A. M. Mendonsa, T.-Y. Na, and B. M. Gumbiner (2018). E-cadherin in contact inhibition and cancer. Oncogene 37 (35), 4769–4780.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  35. 35.

    K. M. Mrozik, O. W. Blaschuk, C. M. Cheong, A. C. W. Zannettino, and K. Vandyke (2018). N-cadherin in cancer metastasis, its emerging role in haematological malignancies and potential as a therapeutic target in cancer. BMC Cancer 18 (1), 939–939.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  36. 36.

    X. Liu, P. Su, S. Meng, M. Aschner, Y. Cao, W. Luo, G. Zheng, and M. Liu (2017). Role of matrix metalloproteinase-2/9 (MMP2/9) in lead-induced changes in an in vitro blood-brain barrier model. Int. J. Biol. Sci. 13 (11), 1351–1360.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  37. 37.

    L. Qian, B. Xie, Y. Wang, and J. Qian (2015). Amygdalin-mediated inhibition of non-small cell lung cancer cell invasion in vitro. Int. J. Clin. Exp. Pathol. 8 (5), 5363–5370.

    PubMed  PubMed Central  Google Scholar 

  38. 38.

    Z. Wang, K. Fang, G. Wang, X. Guan, Z. Pang, Y. Guo, Y. Yuan, N. Ran, Y. Liu, and F. Wang (2019). Protective effect of amygdalin on epithelial-mesenchymal transformation in experimental chronic obstructive pulmonary disease mice. Phytother. Res. 33 (3), 808–817.

    CAS  Article  PubMed  Google Scholar 

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This manuscript was supported by Tabriz University of Medical Sciences. Authors would like to thank Tabriz University of Medical Sciences for financial supporting of this project (Grant Number 61976).


This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

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Mosayyebi, B., Imani, M., Mohammadi, L. et al. Comparison Between β-Cyclodextrin-Amygdalin Nanoparticle and Amygdalin Effects on Migration and Apoptosis of MCF-7 Breast Cancer Cell Line. J Clust Sci (2021).

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  • Amygdalin
  • β-cyclodextrin
  • Migration
  • Breast cancer
  • Apoptosis