PAMAM Dendrimers Augment Inhibitory Effects of Curcumin on Cancer Cell Proliferation: Possible Inhibition of Telomerase

  • Mollazade, Mahdie (Tuberculosis and Lung Research Center, Tabriz University of Medical Sciences) ;
  • Nejati-Koshki, Kazem (Department of Medical Biotechnology, Faculty of Advanced Medical Science, Tabriz University of Medical Sciences) ;
  • Akbarzadeh, Abolfazl (Department of Medical Nanotechnology, Faculty of Advanced Medical Science, Tabriz University of Medical Sciences) ;
  • Zarghami, Nosratollah (Tuberculosis and Lung Research Center, Tabriz University of Medical Sciences) ;
  • Nasiri, Marzieh (Department of Medical Biotechnology, Faculty of Advanced Medical Science, Tabriz University of Medical Sciences) ;
  • Jahanban-Esfahlan, Rana (Department of Medical Biotechnology, Faculty of Advanced Medical Science, Tabriz University of Medical Sciences) ;
  • Alibakhshi, Abbas (Department of Medical Biotechnology, Faculty of Advanced Medical Science, Tabriz University of Medical Sciences)
  • Published : 2013.11.30


Background: Despite numerous useful anticancer properties of curcumin, its utility is limited due to its hydrophobic structure. In this study, we investigated the comparative antiproliferative effect of PAMAM encapsulating curcumin with naked curcumin on the T47D breast cancer cell line. Materials and Methods: Cytotoxic effects of PAMAM dendrimers encapsulating curcumin and curcumin alone were investigated by MTT assay. After treating cells with different concentrations of both curcumin alone and curcumin encapsulated for 24h, telomerase activity was determined by TRAP assay. Results: While PAMAM dendrimers encapsulating curcumin had no cytotoxicity on cancer cells, they decreased the $IC_{50}$ for proliferation and also increased the inhibitory effect on telomerase activity. Conclusions: Considering the non-toxicity in addition to effectiveness for enhancing curcumin anticancer properties, dendrimers could be considered good therapeutic vehicles for this hydrophobic agent.


Dendrimer;curcumin;telomerase;proliferation;breast cancer


  1. Adam Maciejczyk A (2013). New prognostic factors in breast cancer. Adv Clin Exp Med, 22, 5-15.
  2. Alemdaroglu FE, Alemdaroglu NC, Langguth P, et al (2008). DNA block copolymer micelles- a combinatorial tool for cancer nanotechnology. Adv Mater, 20, 899-02.
  3. Anand P, Thomas Sh, Kunnumakkara AB, et al (2008). Biological activities of curcumin and its analogues (congeners) made by man and mother nature. Biochem Pharmacol, 76, 1590-611.
  4. Araujo C, Leon L (2011). Biological activities of Curcuma longa L. Mem Inst Oswaldo Cruz, 96, 723-8.
  5. Bengmark S, Mesa D, Gil A (2009). Plant-derived health- the effects of turmeric and curcuminoids. Nutr Hosp, 24, 273-81.
  6. Bharali B, Khalil M, Gurbuz M, et al (2009). Nanoparticles and cancer therapy: a concise review with emphasis on dendrimers. Int J Nanomedicine, 4, 1-7.
  7. Bisht S, Feldmann G, Soni Sh, et al (2007). Polymeric nanoparticle-encapsulated curcumin ("nanocurcumin"): a novel strategy for human cancer therapy. J Nanobiotechnology, 5, 3.
  8. Cui SH, Qu X, Xie Y, et al (2006). Curcumin inhibits telomerase activity in human cancer cell lines. Int J Mol Med, 18, 227-31.
  9. Gasparini G, Longo R, Torino F, Morabito A (2005). Therapy of breast cancer with molecular targeting agents. Ann Oncol, 16, 28-36.
  10. Herbert B, Wright WE, Shay JW (2001). Telomerase and breast cancer. Breast Cancer Res, 3, 146-9.
  11. Hsina I, Sheu G, Chen HL, et al (2010). N-acetyl cysteine mitigates curcumin-mediated telomerase inhibition through rescuing of Sp1 reduction in A549 cells. Mutat Res, 688, 72-7.
  12. Jemal A, Bray FM, Center M, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90.
  13. Jurenka JS (2009). Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review of preclinical and clinical research. Alt Med Rev, 14, 141-52.
  14. Korkola J, Gray JW (2010). Breast cancer genomes - form and function. Curr Opin Genet Dev, 20, 4-14.
  15. Liu D, Hu H, Zhang J, et al (2011). Drug pH-sensitive release in vitro and targeting ability of polyamidoamine dendrimer complexes for tumor cells. Chem Pharm Bull, 59, 63-71.
  16. Morgan MT, Carnahan MA, Immoos SE, et al (2003). Dendritic molecular capsules for hydrophobic compounds. J Am Chem Soc, 125, 15485-9.
  17. Mukai H (2010). Targeted therapy in breast cancer: current status and future directions. Jpn J Clin Oncol, 40, 711-6.
  18. Nasiri M, Zarghami N, Nejati Koshki K, et al (2013). Curcumin and silibinin inhibit telomerase expression in T47D human breast cancer cells. Asian Pac J Cancer Prev, 14, 3449-53.
  19. Nomani A, Haririan I, Rahimnia R, et al (2010). Physicochemical and biological properties of self-assembled antisense/poly (amidoamine) dendrimer nanoparticles: the effect of dendrimer generation and charge ratio. Int J Nanomedicine, 5, 359-69.
  20. Nejati-Koshki K, Akbarzadeh A, Pourhasan-Moghadam M, et al (2013). Inhibition of leptin and leptin receptor gene expression by silibinin- curcumin combination. Asian Pac J Cancer Prev, 14, [Epub Ahead of print].
  21. Patil ML, Zhang M, Taratula O, et al (2009). Internally cationic polyamidoamine PAMAM-OH dendrimers for siRNA delivery: effect of the degree of quaternization and cancer targeting. Biomacromolecules, 10, 258-66.
  22. Ringman JM, Frautschy SA, Cole GM, et al (2005). A potential role of the curry spice curcumin in alzheimer disease. Curr Alzheimer Res, 2, 131-6.
  23. Shi W, Dolai S, Rizk S (2007). Synthesis of monofunctional curcumin derivatives, clicked curcumin dimer, and a PAMAM dendrimer curcumin conjugate for therapeutic applications. Org Lett, 9, 5461-4.
  24. Wang P, Zhao X, Wang Zh, et al (2010). Generation 4 polyamidoamine dendrimers is a novel candidate of nano-carrier for gene delivery agents in breast cancer treatment. Cancer Lett, 298, 34-49.
  25. Winnicka K, Bielawski K, Bielawska A (2010). Synthesis and cytotoxic activity of G3 PAMAM-NH2 dendrimer-modified digoxin and proscillaridin A conjugates in breast cancer cells. Pharmacol Rep, 62, 414-23.

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