DOI QR코드

DOI QR Code

Inhibitory Effects of β-Cyclodextrin-Helenalin Complexes on H-TERT Gene Expression in the T47D Breast Cancer Cell Line - Results of Real Time Quantitative PCR

  • Ghasemali, Samaneh (Drug Applied Research Center, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences) ;
  • Nejati-Koshki, Kazem (Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences) ;
  • Akbarzadeh, Abolfazl (Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences) ;
  • Tafsiri, Elham (Biotechnology Research Center, Molecular Medicine Department, Pasteur Institute of Iran) ;
  • Zarghami, Nosratollah (Drug Applied Research Center, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences) ;
  • Rahmati-Yamchi, Mohamad (Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences) ;
  • Alizadeh, Effat (Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences) ;
  • Barkhordari, Amin (Drug Applied Research Center, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences) ;
  • Tozihi, Majid (Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences) ;
  • Kordi, Shirafkan (Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences)
  • Published : 2013.11.30

Abstract

Background: Nowadays, the encapsulation of cytotoxic chemotherapeutic agents is attracting interest as a method for drug delivery. We hypothesized that the efficiency of helenalin might be maximized by encapsulation in ${\beta}$-cyclodextrin nanoparticles. Helenalin, with a hydrophobic structure obtained from flowers of Arnica chamissonis and Arnica Montana, has anti-cancer and anti-inflammatory activity but low water solubility and bioavailability. ${\beta}$-Cyclodextrin (${\beta}$-CD) is a cyclic oligosaccharide comprising seven D-glucopyranoside units, linked through 1,4-glycosidic bonds. Materials and Methods: To test our hypothesis, we prepared ${\beta}$-cyclodextrin-helenalin complexes to determine their inhibitory effects on telomerase gene expression by real-time polymerase chain reaction (q-PCR) and cytotoxic effects by colorimetric cell viability (MTT) assay. Results: MTT assay showed that not only ${\beta}$-cyclodextrin has no cytotoxic effect on its own but also it demonstrated that ${\beta}$-cyclodextrin-helenalin complexes inhibited the growth of the T47D breast cancer cell line in a time and dose-dependent manner. Our q-PCR results showed that the expression of telomerase gene was effectively reduced as the concentration of ${\beta}$-cyclodextrin-helenalin complexes increased. Conclusions: ${\beta}$-Cyclodextrin-helenalin complexes exerted cytotoxic effects on T47D cells through down-regulation of telomerase expression and by enhancing Helenalin uptake by cells. Therefore, ${\beta}$-cyclodextrin could be superior carrier for this kind of hydrophobic agent.

Keywords

Helenalin;Telomerase;real time quantitative PCR;${\beta}$-cyclodextrin

References

  1. Atwood JL, Davies JED, MacNicol DD, et al (1996). Comprehensive Supramolecular Chemistry. Oxford Pergamon, 1-10.
  2. Cui SH (2006). Curcumin inhibits telomerase activity in human cancer cell lines. Int J Mol Med, 18, 227-31.
  3. Del Valle EMM (2004). Cyclodextrins and their uses: a review. Process Biochem, 39, 1033-46. https://doi.org/10.1016/S0032-9592(03)00258-9
  4. Feng J, Funk WD, Wang SS, et al (1995). The RNA component of human telomerase. Science, 269, 1236-41. https://doi.org/10.1126/science.7544491
  5. Hahn WC, Stewart SA, Brooks MW, et al (1999). Inhibition of telomerase limits the growth of human cancer cells. Nat Med, 5, 1164-70. https://doi.org/10.1038/13495
  6. Herbet B, Wright WE, Shaly J (2001). Telomerase and breast cancer. Breast cancer Res, 3, 146-9. https://doi.org/10.1186/bcr288
  7. Huang PR, Yeh YM, V Wang TC (2005). Potent inhibition of human telomerase by Helenalin. Cancer Lett, 227, 169-74. https://doi.org/10.1016/j.canlet.2004.11.045
  8. Hsina I, Sheua G, Chena H, et al (2010). N-acetyle cysteine mitigates curcumin-mediated telomerase inhibition through rescuing of SP1 reduction in A549 cells. Mut Res, 688, 72-7. https://doi.org/10.1016/j.mrfmmm.2010.03.011
  9. Jurenka J (2009). Anti-inflammatory properties of curcumin, a major constituent of curcuma longa: a review of preclinical and clinical research. Alter Med Rev, 14, 141-52.
  10. Kirkpatrick KL, Newbold RF, Mokbel k (2004). The mRNA expression of hTERT in human breast carcinomas correlates with VEGF expression. J Carcinogenesis, 147, 3-1.
  11. Kirkpatrick KL, Ogunkolade W, Elkak AE, et al (2003). hTERT expression in human breast cancer and noncancerous breast tissue: correlation withtumor stage and c-Myc expression. Breast Cancer Res. Treatment, 77, 277-84.
  12. Kondo S, Kondo Y, Li G, et al (1998). Targeted therapy of human malignant glioma in a mouse model by 2-5A antisense directed against telomerase RNA, Oncogene. Genes Dev, 16, 3323-30.
  13. Lyss G, Knorre A, Schmidt TJ, et al (1998). The anti-inflammatory sesquiterpene lactone Helenalin inhibits the transcription factor NF-kappa B by directly targeting p65. J Biol Chem, 273, 33508-16. https://doi.org/10.1074/jbc.273.50.33508
  14. Mokbel K (2000). The role of telomerase in breast cancer. Eur J Surg Onco, 26, 509-14. https://doi.org/10.1053/ejso.1999.0932
  15. Murali MY, Jaggi S, Chauhan C (2010).$\beta$-Cyclodextrin-curcumin self-assembly enhances curcumin delivery in prostate cancer cells. Colloids Surf B Biointerfaces, 79, 113-25. https://doi.org/10.1016/j.colsurfb.2010.03.039
  16. Nasiri M, Zarghami N, Koshki KN, et al (2013). Curcumin and silibinin inhibit telomerase expression in T47D human breast cancer cells. Asian Pac J Cancer Prev, 14, 3449-53. https://doi.org/10.7314/APJCP.2013.14.6.3449
  17. Saretzki G (2003). Telomerase inhibition as cancer therapy. Cancer Lett, 194, 209-19. https://doi.org/10.1016/S0304-3835(02)00708-5
  18. Schramm G, Surmann EM, Wiesberg S, et al (2010). Analyzing the regulation of metabolic pathways in human breast cancer. BMC Medical Genomics, 2, 3-5.
  19. Seidel RW, Koleva BB (2009). $\beta$-Cyclodextrin 10.41-hydrate, Acta Crystallogr Sect E Struct Rep Online, 21, 162-3.
  20. Shay JW, Gazdar AF (1997). Telomerase in the early detection of cancer. J Clin Pathol, 50, 106-9. https://doi.org/10.1136/jcp.50.2.106
  21. Tian N, Gaines WJ, Benjamin ZF (2010). Female breast cancermortality clusters within racial groups in the United States. Health Place, 16, 209-18. https://doi.org/10.1016/j.healthplace.2009.09.012
  22. Torkanyi I, Aradi J (2008). Pharmacological intervention strategies for affecting telomerase activity. Future prospects to treat cancer and degenerative disease. Biochimie, 90, 156-72. https://doi.org/10.1016/j.biochi.2007.09.002
  23. Tyagi AK, Agarwal C, Chan DCF, et al (2003). Synergistic anti-cancer effects of silibinin with conventional cytotoxic agents doxorubicin, cisplatin and carboplatin against human breast carcinoma MCF-7 and MDA-MB468 cells. Oncol Rep, 11, 493-99.
  24. Vivek RY, Sarasija S, Kshama D, et al (2009). Effect of Cyclodextrin complexation of curcumin on its solubility and antiangiogenic sand anti-inflammatory activity in rat colitis model. AAPS. Pharm Sci Tech, 10, 233-44.
  25. Zhang X, Mar V, Zhou W, et al (1999). Telomere shortening and apoptosis, in telomerase-inhibited human tumor cells. Genes Dev, 13, 2388-99. https://doi.org/10.1101/gad.13.18.2388

Cited by

  1. Magnetic Nanocomposites Based on Poly(N-isopropylacrylamide) for Anti-cancer Drug Delivery vol.15, pp.1, 2014, https://doi.org/10.7314/APJCP.2014.15.1.49
  2. Molecular Target Therapy of AKT and NF-kB Signaling Pathways and Multidrug Resistance by Specific Cell Penetrating Inhibitor Peptides in HL-60 Cells vol.15, pp.10, 2014, https://doi.org/10.7314/APJCP.2014.15.10.4353
  3. Trichostatin A-induced Apoptosis is Mediated by Krüppel-like Factor 4 in Ovarian and Lung Cancer vol.15, pp.16, 2014, https://doi.org/10.7314/APJCP.2014.15.16.6581
  4. Comparison of Inhibitory Effects of 17-AAG Nanoparticles and Free 17-AAG on HSP90 Gene Expression in Breast Cancer vol.15, pp.17, 2014, https://doi.org/10.7314/APJCP.2014.15.17.7113
  5. Silver nanoparticles: Synthesis methods, bio-applications and properties pp.1549-7828, 2014, https://doi.org/10.3109/1040841X.2014.912200
  6. Pectic-Oligoshaccharides from Apples Induce Apoptosis and Cell Cycle Arrest in MDA-MB-231 Cells, a Model of Human Breast Cancer vol.16, pp.13, 2015, https://doi.org/10.7314/APJCP.2015.16.13.5265
  7. Preparation and Evaluation of Chrysin Encapsulated in PLGA-PEG Nanoparticles in the T47-D Breast Cancer Cell Line vol.16, pp.9, 2015, https://doi.org/10.7314/APJCP.2015.16.9.3753
  8. Magnetic nanoparticles: Applications in gene delivery and gene therapy pp.2169-141X, 2015, https://doi.org/10.3109/21691401.2015.1014093
  9. Magnetic nanoparticles as potential candidates for biomedical and biological applications pp.2169-141X, 2015, https://doi.org/10.3109/21691401.2014.998832
  10. Biomedical and biological applications of quantum dots pp.2169-141X, 2015, https://doi.org/10.3109/21691401.2014.998826
  11. Comparison, synthesis and evaluation of anticancer drug-loaded polymeric nanoparticles on breast cancer cell lines pp.2169-141X, 2015, https://doi.org/10.3109/21691401.2015.1008510
  12. Current methods for synthesis of magnetic nanoparticles vol.44, pp.2, 2016, https://doi.org/10.3109/21691401.2014.982802
  13. CellMethy: Identification of a focal concordantly methylated pattern of CpGs revealed wide differences between normal and cancer tissues vol.5, pp.1, 2016, https://doi.org/10.1038/srep18037
  14. Spotlight on 17-AAG as an Hsp90 inhibitor for molecular targeted cancer treatment pp.17470277, 2019, https://doi.org/10.1111/cbdd.13486