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Targeting HSP90 Gene Expression with 17-DMAG Nanoparticles in Breast Cancer Cells

  • Mellatyar, Hassan (Department of Medical Biotechnology, Faculty of Advance Medical Sciences, Tabriz University of Medical Sciences) ;
  • Talaei, Sona (Department of Medical Biotechnology, Faculty of Advance Medical Sciences, Tabriz University of Medical Sciences) ;
  • Nejati-Koshki, Kazem (Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Zanjan University of Medical Sciences) ;
  • Akbarzadeh, Abolfazl (Stem Cell Research Center, Tabriz University of Medical Sciences)
  • Published : 2016.05.01

Abstract

Background: Dysregulation of HSP90 gene expression is known to take place in breast cancer. Here we used D,L-lactic-co-glycolic acid-polyethylene glycol-17-dimethylaminoethylamino-17-demethoxy geldanamycin (PLGA-PEG-17DMAG) complexes and free 17-DMAG to inhibit the expression of HSP90 gene in the T47D breast cancer cell line. The purpose was to determine whether nanoencapsulating 17DMAG improves the anti-cancer effects as compared to free 17DMAG. Materials and Methods: The T47D breast cancer cell line was grown in RPMI 1640 supplemented with 10% FBS. Encapsulation of 17DMAG was conducted through a double emulsion method and properties of copolymers were characterized by Fourier transform infrared spectroscopy and H nuclear magnetic resonance spectroscopy. Assessment of drug cytotoxicity was by MTT assay. After treatment of T47D cells with a given amount of drug, RNA was extracted and cDNA was synthesized. In order to assess HSP90 gene expression, real-time PCR was performed. Results: Taking into account drug load, IC50 was significant decreased in nanocapsulated 17DMAG in comparison with free 17DMAG. This finding was associated with decrease of HSP90 gene expression. Conclusions: PLGA-PEG-17DMAG complexes can be more effective than free 17DMAG in down-regulating of HSP90 expression, at the saesm time exerting more potent cytotoxic effects. Therefore, PLGA-PEG could be a superior carrier for this type of hydrophobic agent.

Keywords

Breast cancer;HSP90;17DMAG-PLGA-PEG;T47D cell line

Acknowledgement

Supported by : Hematology and Oncology Research Center, Tabriz University of Medical Sciences

References

  1. Arpino G, Bardou VJ (2004). Infiltrating lobular carcinoma of the breast: tumor characteristics and clinical outcome.Breast Cancer Res, 6, 149-56. https://doi.org/10.1186/bcr767
  2. Bojesen S, Pooley KA (2013). Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer. Nat Genet, 45, 371-84. https://doi.org/10.1038/ng.2566
  3. Davaran S, Alimirzalu S, Nejati-Koshki K, et al (2014). Synthesis and study of physicochemical characteristics of Fe3O4 magnetic nanocomposites based on poly (Nisopropylacrylamide) for anti-cancer drugs delivery. Asian Pac J Cancer Prev, 15, 49-54. https://doi.org/10.7314/APJCP.2014.15.1.49
  4. Davoudi Z, Akbarzadeh A, Rahmatiyamchi M, et al (2014). Molecular target therapy of AKT and NF-kB signaling pathways and multidrug resistance by specific cell penetrating inhibitor peptides in HL-60 Cells. Asian Pac J Cancer Prev, 15, 4353-8. https://doi.org/10.7314/APJCP.2014.15.10.4353
  5. Dilnawaz F, Singh A, et al (2010). Dual drug loaded superparamagnetic iron oxide nanoparticles for targeted cancer therapy. Biomaterials, 31, 3694-706. https://doi.org/10.1016/j.biomaterials.2010.01.057
  6. Dobo C, Stavale JN, Lima Fde O, et al (2013). HSP27 is Commonly Expressed in Cervical Intraepithelial Lesions of Brazilian Women. Asian Asian Pac J Cancer Prev, 14, 5007-10. https://doi.org/10.7314/APJCP.2013.14.9.5007
  7. Early Early Breast Cancer Trialists' Collaborative Group (EBCTCG), Darby S, McGale P, et al (2011). Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10801 women in 17 randomised trials. Lancet, 378, 1707-16. https://doi.org/10.1016/S0140-6736(11)61629-2
  8. Ghasemali S, Nejati-Koshki K, Tafsiri E, et al (2013). Study of Inhibitory Effect of ${\beta}$-Cyclodextrin-HelenalinComplex on HTERT Gene Expression in T47D Breast Cancer Cell Line by Real Time Quantitative PCR (q-PCR). Asian Pac J Cancer Prev, 14, 6949-53. https://doi.org/10.7314/APJCP.2013.14.11.6949
  9. Goldhirsch A, Wood WC (2011). Strategies for subtypes-dealing with the diversity of breast cancer: highlights of the st gallen international expert consensus on the primary therapy of early breast cancer 2011. Ann Oncol, 22, 1736-47. https://doi.org/10.1093/annonc/mdr304
  10. Guo W, Siegel D, Ross D, et al (2008). Stability of the Hsp90 inhibitor 17AAG hydroquinone and prevention of metal catalyzed oxidation. J Pharm Sci, 97, 5147-57 https://doi.org/10.1002/jps.21394
  11. Hosseininasab S, Pashaei-Asl R, Khandaghi AA, et al (2014). Synthesis, characterization, and in vitro studies of PLGA-PEG nanoparticles for oral insulin delivery. Chem Biol Drug Des, 84, 307-15. https://doi.org/10.1111/cbdd.12318
  12. Karkoulis PK, Stravopodis DJ (2010). 17-Allylamino-17-demethoxygeldanamycin induces downregulation of critical Hsp90 protein clients and results in cell cycle arrest and apoptosis of human urinary bladder cancer cells. BMC Cancer, 10, 481. https://doi.org/10.1186/1471-2407-10-481
  13. Lindgren M, Rosenthal-Aizman K, et al (2006). Overcoming methotrexate resistance in breast cancer tumour cells by the use of a new cell penetrating peptide. Biochem Pharmacol, 71, 416-25. https://doi.org/10.1016/j.bcp.2005.10.048
  14. Makhnevych T, Houry WA (2012). The role of Hsp90 in protein complex assembly. Biochim Biophys Acta, 1823, 674-82. https://doi.org/10.1016/j.bbamcr.2011.09.001
  15. Mestril R, Batey J (2014). Heat shock proteins protect skeletal muscle against frostbite injury. FASEB J, 28, 1102-43.
  16. Nejati-Koshki K, Akbarzadeh A, Pourhasan-Moghaddam M, et al (2014). Inhibition of leptin and leptin receptor gene expression by silibinin-curcumin combination. Asian Pac J Cancer Prev, 14, 6595-9.
  17. Nejati-Koshki K, Zarghami N, Pourhassan-Moghaddam M, et al (2012). Inhibition of leptin gene expression and secretion by silibinin: possible role of estrogen receptors. Cytotechnol, 64, 719-26. https://doi.org/10.1007/s10616-012-9452-3
  18. Nejati-Koshki K, Mesgari M, Ebrahimi E, Abbasalizadeh F, et al (2014). Synthesis and in vitro study of cisplatin-loaded Fe3O4 nanoparticles modified with PLGA-PEG6000 copolymers in treatment of lung cancer. J Microencapsul, 31, 815-23. https://doi.org/10.3109/02652048.2014.940011
  19. Pourhassan-Moghaddam M, Rahmati-Yamchi M, Akbarzadeh A, et al (2013). Protein detection through different platforms of immuno-loop-mediated isothermal amplification. Nanoscale Research Letters, 8, 485. https://doi.org/10.1186/1556-276X-8-485
  20. Qu Zh, Dong H, et al (2013). Combined effects of 17-DMAG and TNF on cells through a mechanism related to the NF-kappaB pathway. Diagn Pathol, 8, 70.
  21. Rohl A, Rohrberg J, et al (2013). The chaperone Hsp90: changing partners for demanding clients. Trends Biochem Sci, 38, 253-62. https://doi.org/10.1016/j.tibs.2013.02.003
  22. Sadat Tabatabaei Mirakabad F, Nejati-Koshki K, Akbarzadeh A, et al (2014). PLGA-based nanoparticles as cancer drug delivery systems. Asian Pac J Cancer Prev, 15, 517-35. https://doi.org/10.7314/APJCP.2014.15.2.517
  23. Sharp S, Workman P (2006). Inhibitors of the HSP90 molecular chaperone: current status. Adv Cancer Res, 95, 323-348.
  24. Sun X, Bristol JA, et al (2013). Hsp90 Inhibitor 17-DMAG decreases expression of conserved herpesvirus protein kinases and reduces virus production in Epstein-Barr virus-infected cells. J Virol, 87, 10126-38. https://doi.org/10.1128/JVI.01671-13
  25. Tanaka T, Decuzzi P, Cristofanilli M, et al (2009). Nanotechnology for breast cancer therapy. Biomed Microdevices, 11, 49-63. https://doi.org/10.1007/s10544-008-9209-0
  26. Toikkanen S, Pylkkanen L, Joensuu H, et al (1997). Invasive lobular carcinoma of the breast has better short- and long-term survival than invasive ductal carcinoma. Br J Cancer, 79, 1234-40.
  27. Virnig BA, Tuttle TM, Shamliyan T, et al (2010). Ductal carcinoma in situ of the breast: a systematic review of incidence, treatment, and outcomes. J Natl Cancer Inst, 102, 170-8. https://doi.org/10.1093/jnci/djp482
  28. Whitesell L, Lindquist SL (2005). HSP90 and the chaperoning of cancer. Nat Rev Cancer, 5, 761-772. https://doi.org/10.1038/nrc1716
  29. Wu GQ, Liu NN, Xue XL, et al (2014). Multiplex Real-time PCR for RRM1, XRCC1, TUBB3 and TS mRNA for prediction of response of non-small cell lung cancer to chemoradiotherapy. Asian Pac J Cancer Prev, 15, 4153-8. https://doi.org/10.7314/APJCP.2014.15.10.4153
  30. Zhang X, Hanamura N, Yamasita M, et al (2011). A case of lobular carcinoma in Situ presenting as a solid mass. Br J Radiol, 84, 48-50.