Asian Pacific Journal of Cancer Prevention

  • 제15권10호
  • /
  • Pages.4353-4358
  • /
  • 2014
  • /
  • 1513-7368(pISSN)
  • /
  • 2476-762X(eISSN)
아시아태평양암예방학회 (Asian Pacific Journal of Cancer Prevention)
권호 표지
DOI QR코드

DOI QR Code

Molecular Target Therapy of AKT and NF-kB Signaling Pathways and Multidrug Resistance by Specific Cell Penetrating Inhibitor Peptides in HL-60 Cells

  • Davoudi, Zahra (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) ;
  • Rahmatiyamchi, Mohammad (Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences) ;
  • Movassaghpour, Ali Akbar (Hematology and Oncology Research Center, Tabriz University of Medical Sciences) ;
  • Alipour, Mohsen (Department of Physiology, Faculty of Medicine, Zanjan University of Medical Sciences) ;
  • Nejati-Koshki, Kazem (Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences) ;
  • Sadeghi, Zohre (Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences) ;
  • Dariushnejad, Hassan (Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences) ;
  • Zarghami, Nosratollah (Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences)
  • 발행 : 2014.05.30
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Background: PI3/AKT and NF-kB signaling pathways are constitutively active in acute myeloid leukemia and cross-talk between the two has been shown in various cancers. However, their role in acute myeloid leukemia has not been completely explored. We therefore used cell penetrating inhibitor peptides to define the contributions of AKT and NF-kB to survival and multi drug resistance (MDR) in HL-60 cells. Materials and Methods: Inhibition of AKT and NF-kB activity by AKT inhibitor peptide and NBD inhibitor peptide, respectively, resulted in decreased expression of mRNA for the MDR1 gene as assessed by real time PCR. In addition, treatment of HL-60 cells with AKT and NBD inhibitor peptides led to inhibition of cell viability and induction of apoptosis in a dose dependent manner as detected by flow cytometer. Results: Finally, co-treatment of HL-60 cells with sub-optimal doses of AKT and NBD inhibitor peptides led to synergistic apoptotic responses in AML cells. Conclusions: These data support a strong biological link between NF-kB and PI3-kinase/AKT pathways in the modulation of antiapoptotic and multi drug resistant effects in AML cells. Synergistic targeting of these pathways using NF-kB and PI3-kinase/AK inhibitor peptides may have a therapeutic potential for AML and possibly other malignancies with constitutive activation of these pathways.

키워드

참고문헌

  1. Akbarzadeh A, Ghasemali S, Nejati K, et al (2013). Study of inhibitory effect of $\beta$-cyclodextrin-helenalin complex 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
  2. Akbarzadeh A, Hosseininasab S, Davaran S, et al (2014). Synthesis, characterization, and In vitro studies of PLGAPEG nanoparticles for oral Insulin delivery. Chem Biol Drug Des, 3, 1-9.
  3. Akbarzadeh A, Mikaeili H, Zarghami N, et al (2012). Preparation and in-vitro evaluation of doxorubicin-loaded Fe3O4 magnetic nanoparticles modified with biocompatible copolymer. Int J Nanomedicine, 7, 1-16. https://doi.org/10.2217/nnm.11.171
  4. Akbarzadeh A, Nejati-Koshki K, Mahmoudi Soghrati M, et al (2013). In vitro studies of NIPAAM-MAA-VP copolymercoated magnetic nanoparticles for controlled anticancer drug release. JEAS, 3, 108-15. https://doi.org/10.4236/jeas.2013.34013
  5. Akbarzadeh A, Omidfar K, Ahmadin A, et al (2014). An electrochemical immunosensor for digoxin using core-shell gold coated magnetic nanoparticles as labels. Mol Biol Rep, 41, 1659-68. https://doi.org/10.1007/s11033-013-3014-4
  6. Akbarzadeh A, Pourhassan-Moghaddam M, Rahmati-Yamchi M, et al (2013). Protein detection through different platforms of immuno-loop-mediated isothermal amplification. Nanoscale Res Lett, 8, 485-95. https://doi.org/10.1186/1556-276X-8-485
  7. Akbarzadeh A, Rezaei A, Nejati-Koshki K, et al (2014). Synthesis and physicochemical characterization of biodegradable star-shaped poly lactide-co-glycolide- $\beta$-cyclodextrin copolymer Nanoparticles Containing Albumin, J Adv Nanoparticles, 3, 1-9. https://doi.org/10.4236/anp.2014.31001
  8. Akbarzadeh A, Rezaei-Sadabady R, Zarghami N, et al (2013). Studies of the relationship between structure and antioxidant activity in interesting systems, including tyrosol, hydroxytyrosol derivatives indicated by quantum chemical calculations. Soft, 2, 13-8. https://doi.org/10.4236/soft.2013.23004
  9. Akbarzadeh A, Samiei M, Davaran S, et al (2012). Magnetic nanoparticles: preparation, physical properties, and applications in biomedicine. Nanoscale Res Lett, 7, 14-26. https://doi.org/10.1186/1556-276X-7-14
  10. Akbarzadeh A, Samiei M, Joo SW, et al (2012). Synthesis, characterization and in vitro studies of doxorubicin-loaded magnetic nanoparticles grafted to smart copolymers on A549 lung cancer cell line. J Nanobiotechnol, 10, 46-52. https://doi.org/10.1186/1477-3155-10-46
  11. Akbarzadeh A, Zarghami N, Mikaeili H, et al (2012). Synthesis, characterization and in vitro evaluation of novel polymercoated magnetic nanoparticles for controlled delivery of doxorubicin. Nanotechnol Sci Appl, 5, 13-25.
  12. Al-Bahar S, Adriana Z, Pandita R (2008). Acute myeloid leukemia as a genetic disease. Gulf J Oncolog, 3, 9-15.
  13. Altman JK, Sassano A, Platanias LC (2011). Targeting mTOR for the treatment of AML: New agents and new directions. Oncotarge, 2, 510-7.
  14. Bentires-Alj M, Barbu V, Fillet M, et al (2003). NF-kB transcription factor induces drug resistance through MDR1expression in cancer cells. Oncogene, 22, 90-7. https://doi.org/10.1038/sj.onc.1206056
  15. Birkenkamp KU, Geugien M, Schepers H, et al (2004). Constitutive NF-jB DNA-binding activity in AML is frequently mediated by a Ras/PI3-K/PKB-dependent pathway. Leukemia, 18, 103-12. https://doi.org/10.1038/sj.leu.2403145
  16. Bixby D, Talpaz M (2009). Mechanisms of resistance to tyrosine kinase inhibitors in chronic myeloid leukemia and recent therapeutic strategies to overcome resistance. Hematol Am Soc Hematol Educ Program, 1, 461-76.
  17. Caceres-Cortes JR (2013). Blastic Leukaemias (AML) :A Biologist s view. Cell Biochem Biophys, 66, 13-22. https://doi.org/10.1007/s12013-012-9392-8
  18. Chuang JC, Sheu GT, Wang PC, et al (2012). Docetaxel and 5-fluorouracil induce human p53 tumor suppressor gene transcription via a short sequence at core promoter element. Toxicol in Vitro, 26, 678-85. https://doi.org/10.1016/j.tiv.2012.03.004
  19. Ebrahimnezhad Z, Zarghami N, Keyhani M, et al (2013). Inhibition of hTERT gene expression by silibinin-loaded PLGA-PEG-Fe3O4 in T47D breast cancer cell line. Bioimpacts, 3, 67-74.
  20. Eldar-Finkelman H, Eisenstein M (2009). Peptide inhibitors targeting protein kinases. Curr Pharm Des, 15, 2463-70. https://doi.org/10.2174/138161209788682253
  21. Furumai R, Komatsu Y, Nishino N, et al. (2001). Potent histone deacetylase inhibitors built from trichostatin. Proc Natl Acad Sci USA, 98, 87-92. https://doi.org/10.1073/pnas.98.1.87
  22. Grandage VL, Gale RE, et al (2005). PI3-kinase/Akt is constitutively active in primary acute myeloid leukaemia cells and regulates survival and chemoresistance via NFkB, MAPkinase and p53 pathways. Leukemia, 19, 586-94.
  23. Harris F, Dennison SR, Singh J, et al (2013). On the selectivity and efficacy of defense peptides with respect to cancer cells. Med Res Re, 33, 190-234. https://doi.org/10.1002/med.20252
  24. Kumar CC, Madison V (2005). AKT crystal structure and AKTspecific inhibitors. Oncogene, 24, 7493-501. https://doi.org/10.1038/sj.onc.1209087
  25. Leith CP, Kopecky KJ, Godwin J, et al (1997). Acute myeloid leukemia in the elderly: assessment of multidrug resistance (MDR1) and cytogenetics distinguishes biologic subgroups with remarkably distinct responses to standard chemotherapy ASouthwest Oncology Group Study. Blood, 89, 3323-9.
  26. Levitzki A, Klein S (2010). Signal transduction therapy of cancer. Mol Aspects Med, 31, 287-329. https://doi.org/10.1016/j.mam.2010.04.001
  27. Licht JD, Sternberg DW (2005). The molecular pathology of acute myeloid leukemia. Hematol Am Soc Hematol Educ Program, 1, 137-42.
  28. Lowenberg B, Downing J, Burnett A (1999). Acute myeloid leukaemia. N Engl J Med, 341, 1051-62. https://doi.org/10.1056/NEJM199909303411407
  29. Caceres-Cortes JR (2013). Blastic leukaemias (AML): a biologist s view. Cell Biochem Biophys, 66, 13-22. https://doi.org/10.1007/s12013-012-9392-8
  30. Miyamoto S (2011). Nuclear initiated NF-$\kappa{B}$ signaling: NEMO and ATM take center stage. Cell Res, 21, 116-30. https://doi.org/10.1038/cr.2010.179
  31. Mollazade M, Nejati-Koshki K, Akbarzadeh A, et al (2013). PAMAM dendrimers augment inhibitory effects of curcumin on cancer cell proliferation: possible inhibition of telomerase. Asian Pac J Cancer Prev, 14, 6925-8. https://doi.org/10.7314/APJCP.2013.14.11.6925
  32. 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. Cytotechnology, 64, 719-26. https://doi.org/10.1007/s10616-012-9452-3
  33. Nejati-Koshki K, Akbarzadeh A, Pourhasan-Moghaddam M, et al (2013). Inhibition of leptin and leptin receptor gene expression by silibinin-curcumin combination. Asian Pac J Cancer Prev, 14, 6595-9. https://doi.org/10.7314/APJCP.2013.14.11.6595
  34. 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
  35. Norgaard JM, Hokland P (2000). Biology of multiple drug resistance in acute leukemia. Int J Hematol, 72, 290-7.
  36. Orange JS, May MJ (2008). Cell penetrating peptide inhibitors of Nuclear Factor-kappa B. Cell Mol Life Sci, 65, 3564-91. https://doi.org/10.1007/s00018-008-8222-z
  37. Park S, Chapuis N, Tamburini J, et al (2010). Role of the PI3K/AKT and mTOR signaling pathways in acute myeloid leukemia. Haematologica, 95, 819-28. https://doi.org/10.3324/haematol.2009.013797
  38. Siegel R, Naishadham D, Jemal A (2013). Cancer statistics, 2013. CA Cancer J Clin, 63, 11-30. https://doi.org/10.3322/caac.21166
  39. Scholl C, Gilliland DG, Frohling S (2008). Deregulation of signaling pathways in acute myeloid leukemia. Semin Oncol, 35, 336-45. https://doi.org/10.1053/j.seminoncol.2008.04.004
  40. Tas SW, de Jong EC, Hajji N, et al (2005). Selective inhibition of NF-jB in dendritic cells by the NEMO-binding domain peptide blocks maturation and prevents T cell proliferation and polarization. Eur J Immuno, 35, 1164-74. https://doi.org/10.1002/eji.200425956
  41. Ta-Gan Y, Hurevich M, Klein S, et al (2011). Backbone cyclic peptide inhibitors of protein kinase B (PKB/Akt). J Med Chem, 54, 5154-64. https://doi.org/10.1021/jm2003969
  42. Thanos D, Maniatis T (1995). NF-kappa B: a lesson in family values. Ce, 80, 529-32.
  43. Tho F, Ganser A (2011). Molecular pathogenesis of acute myeloid leukemia: a diverse disease with new perspectives. Front Med China, 4, 356-62.
  44. Wang Y, Liu X, Zhang HT, et al (2007). NF-kappaB regulating expression of mdr1 gene and P-gp to reverse drug-resistance in leukemic cells. Zhongguo Shi Yan Xue Ye Xue Za Zhi, 15, 950-4.
  45. Weisburg JH (2008). Multidrug resistance in acute myeloid leukemia: potential new therapeutics. J Nucl Med, 49, 1405-7. https://doi.org/10.2967/jnumed.107.050153
  46. Zeng Z, Sarbassov dos D, Samudio IJ, et al (2007). Rapamycin derivatives reduce mTORC2 signaling and inhibitAKT activation inAML. Blood, 109, 3509-12. https://doi.org/10.1182/blood-2006-06-030833

피인용 문헌

  1. infection vol.14, pp.6, 2015, https://doi.org/10.1586/14760584.2015.1008460
  2. 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
  3. Hurdles in selection process of nanodelivery systems for multidrug-resistant cancer vol.142, pp.10, 2016, https://doi.org/10.1007/s00432-016-2167-7
  4. Effects of Epothilone A in Combination with the Antidiabetic Drugs Metformin and Sitagliptin in HepG2 Human Hepatocellular Cancer Cells: Role of Transcriptional Factors NF-κB and p53 vol.17, pp.3, 2016, https://doi.org/10.7314/APJCP.2016.17.3.993
  5. Current methods for synthesis of magnetic nanoparticles vol.44, pp.2, 2016, https://doi.org/10.3109/21691401.2014.982802
  6. Lp16-PSP, a Member of YjgF/YER057c/UK114 Protein Family Induces Apoptosis and p21WAF1/CIP1 Mediated G1 Cell Cycle Arrest in Human Acute Promyelocytic Leukemia (APL) HL-60 Cells vol.18, pp.11, 2017, https://doi.org/10.3390/ijms18112407
  7. Design of new acid-activated cell-penetrating peptides for tumor drug delivery vol.5, pp.2167-8359, 2017, https://doi.org/10.7717/peerj.3429
  8. Differential effect of psoralidin in enhancing apoptosis of colon cancer cells via nuclear factor-κB and B-cell lymphoma-2/B-cell lymphoma-2-associated X protein signaling pathways vol.11, pp.1, 2015, https://doi.org/10.3892/ol.2015.3861
  9. Circulating microRNA-125b and microRNA-130a expression profiles predict chemoresistance to R-CHOP in diffuse large B-cell lymphoma patients vol.11, pp.1, 2015, https://doi.org/10.3892/ol.2015.3866
  10. Apoptotic Effect of Saccharomyces cerevisiae on Human Colon Cancer SW480 Cells by Regulation of Akt/NF-ĸB Signaling Pathway pp.1867-1314, 2019, https://doi.org/10.1007/s12602-019-09528-7