[Home ] [Archive]   [ فارسی ]  
:: Main :: About us :: Current Issue :: Archive :: Search :: Submit :: Contact ::
Main Menu
Home::
Journal Information::
Articles archive::
For Authors::
For Reviewers::
Subscription::
News& Events::
Contact us::
Site Facilities::
Ethics & Permissions::
::
Search in website

Advanced Search
..
Receive site information
Enter your Email in the following box to receive the site news and information.
..
Indexing
                        
..
:: Volume 15, Issue 2 (Summer 2018) ::
Sci J Iran Blood Transfus Organ 2018, 15(2): 120-132 Back to browse issues page
The effect of telomerase inhibitor MST-312 on apoptosis of acute lymphoblastic leukemia cell line NALM-6
N. Ghasemimehr , Z. Yazdani , A.R. Farsinejad , R. Mirzaee Khalilabadi , A. Fatemi
Keywords: Key words: Telomerase, Apoptosis, Acute Lymphoid Leukemia
Full-Text [PDF 837 kb]   (1294 Downloads)     |   Abstract (HTML)  (4099 Views)
Type of Study: Research | Subject: Hematology
Published: 2018/06/15
Full-Text:   (1962 Views)
References:
 
 
  1. Mei L, Ontiveros EP, Grif EA, Thompson JE, Wang ES, Wetzler M. Blood Reviews Pharmacogenetics predictive of response and toxicity in acute lymphoblastic leukemia therapy. Blood Rev 2015; 29(4): 243-9.
  2. Nesheli HM, Moghaddam TG, Zahedpasha Y, Norouzi AR. Acute Lymphoblastic Leukemia with Eosinophilia and Strongyloides stercoralis Hyperinfection Case Presentation. Iran J Pediatr 2011; 21(4): 549-52.
  3. Pahloosye A, Hashemi A, Mirmohammadi SJ, Atefi A. Presenting Clinical and Laboratory Data of Childhood Acute Lymphoblastic Leukemia. Iran J Pediatr Hematol Oncol 2011; 1(3): 71-7.
  4. Terwilliger T, Abdul-Hay M. Acute lymphoblastic leukemia: a comprehensive review and 2017 update. Blood Cancer J 2017; 7(6): e577.
  5. Healy J, Richer C, Bourgey M, Kritikou EA, Sinnett D. Replication analysis confirms the association of ARID5B with childhood B-cell acute lymphoblastic leukemia. Haematologica 2010; 95(9): 1608-11.
  6. Inaba H, Greaves M, Mullighan CG. Acute lymphoblastic leukaemia. Lancet 2013; 381(9881): 1943-55.
  7. Jabbour E, O’Brien S, Konopleva M, Kantarjian H. New insights into the pathophysiology and therapy of adult acute lymphoblastic leukemia. Cancer 2015; 121(15): 2517-28.
  8. Kato M, Manabe A. Treatment and biology of pediatric acute lymphoblastic leukemia. Pediatr Int 2018; 60(1): 4-12.
  9. Hunger SP, Lu X, Devidas M, Camitta BM, Gaynon PS, Winick NJ, et al. Improved survival for children and adolescents with acute lymphoblastic leukemia between 1990 and 2005: A report from the children’s oncology group. J Clin Oncol 2012; 30(14): 1663-9.
  10. Mar BG, Bullinger LB, McLean KM, Grauman PV, Harris MH, Stevenson K, et al. Mutations in epigenetic regulators including SETD2 are gained during relapse in paediatric acute lymphoblastic leukaemia. Nat Commun 2014; 5: 3469.
  11. Dong X, Liu A, Zer C, Feng J, Zhen Z, Yang M, et al. siRNA inhibition of telomerase enhances the anti-cancer effect of doxorubicin in breast cancer cells. BMC Cancer 2009; 9: 133.
  12. Ruden M, Puri N. Novel anticancer therapeutics targeting telomerase. Cancer Treat Rev 2013; 39(5): 444-56.
  13. Gomez DE, Armando RG, Farina HG, Menna PL, Cerrudo CS, Ghiringhelli PD, et al. Telomere structure and telomerase in health and disease (Review). Int J Oncol 2012; 41(5): 1561-9.
  14. Kustanovich AM, Savitskaya TV, Potapnev MP. Telomerase Activity and Telomere Length in Malignant Cells of Children With Acute Lymphoblastic Leukemia. Exp Oncol 2003; 25(1): 69-73.
  15. Plasschaert SLA, Kamps WA, Vellenga E, de Vries EGE, de Bont ESJM. Prognosis in childhood and adult acute lymphoblastic leukaemia: A question of maturation? Cancer Treat Rev 2004; 30(1): 37-51.
  16. Schneider WC. Phosphorus compounds in animal tissues. I. Extraction and estimation of desoxypentose nucleic acid and of pentose nucleic acid. J Biol Chem 1945; 161: 293-303.
  17. Allsopp RC, Vaziri H, Patterson C, Goldstein S, Younglai E V, Futcher AB, et al. Telomere length predicts replicative capacity of human fibroblasts. Proc Natl Acad Sci U S A 1992; 89(21): 10114-8.
  18. Fatemi A, Safa M, Kazemi A. MST-312 induces G2/M cell cycle arrest and apoptosis in APL cells through inhibition of telomerase activity and suppression of NF-κB pathway. Tumour Biol 2015; 36(11): 8425-37.
  19. Kanno S, Kitajima Y, Kakuta M, Osanai Y, Kurauchi K, Ujibe M, et al. Costunolide-induced apoptosis is caused by receptor-mediated pathway and inhibition of telomerase activity in NALM-6 cells. Biol Pharm Bull 2008; 31(5): 1024-8.
  20. Bashash D, Zareii M, Safaroghli-Azar A, Omrani MD, Ghaffari SH. Inhibition of telomerase using BIBR1532 enhances doxorubicin-induced apoptosis in pre-B acute lymphoblastic leukemia cells. Hematology 2017; 22(6): 330–40.
  21. Serrano D, Bleau AM, Fernandez-Garcia I, Fernandez-Marcelo T, Iniesta P, Ortiz-de-Solorzano C, et al. Inhibition of telomerase activity preferentially targets aldehyde dehydrogenase-positive cancer stem-like cells in lung cancer. Mol Cancer 2011; 10: 96.
  22. Gurung RL, Lim HK, Venkatesan S, Lee PSW, Hande
MP. Targeting DNA-PKcs and telomerase in brain tumour cells. Mol Cancer 2014; 13: 232.
  1. Baerlocher GM, Oppliger Leibundgut E, Ottmann OG, Spitzer G, Odenike O, McDevitt MA, et al. Telomerase Inhibitor Imetelstat in Patients with Essential Thrombocythemia. N Engl J Med 2015; 373(10): 920-8.
  2. Shay JW, Wright WE. Telomerase: a target for cancer therapeutics. Cancer Cell 2002; 2(4): 257-65.
  3. Olaussen KA, Dubrana K, Domont J, Spano JP, Sabatier L, Soria JC. Telomeres and telomerase as targets for anticancer drug development. Crit Rev Oncol Hematol 2006; 57(3): 191-214.
  4. Wong VCH, Ma J, Hawkins CE. Telomerase inhibition induces acute ATM-dependent growth arrest in human
    astrocytomas. Cancer Lett 2009; 274(1): 151-9.
  5. Chung SS, Oliva B, Dwabe S, Vadgama JV. Combination treatment with flavonoid morin and telomerase inhibitor MST-312 reduces cancer stem cell traits by targeting STAT3 and telomerase. Int J Oncol 2016; 49(2): 487-98.
  6. Gurung RL, Lim SN, Low GKM, Hande MP. MST-312 alters telomere dynamics, gene expression profiles and growth in human breast cancer cells. J Nutrigenet Nutrigenomics 2014; 7(4-6): 283-98.
  7. Seimiya H, Oh-hara T, Suzuki T, Naasani I, Shimazaki T, Tsuchiya K, et al. Telomere shortening and growth inhibition of human cancer cells by novel synthetic telomerase inhibitors MST-312, MST-295, and MST-1991. Mol Cancer Ther 2002; 1(9): 657-65.
 
 
 
 
 
 
Sci J Iran Blood Transfus Organ 2018; 15(2): 120-132
Original Article
 
 

 
 

The effect of telomerase inhibitor MST-312 on apoptosis
of  acute lymphoblastic leukemia cell line NALM-6
 
Ghasemimehr N.1, Yazdani Z.1, Farsinejad A.R.1, Mirzaee Khalilabadi R.1, Fatemi A.1
 
 
1Department of Hematology and Medical Laboratory Sciences, Faculty of Allied Medical Sciences, Kerman University of Medical Sciences, Kerman, Iran
 
 
Abstract
Background and Objectives
There have been continuous efforts in telomerase-targeted therapy for cancer treatment because telomerase expression is significantly increased in about 85- 90% of human cancers while its expression is usually silenced in normal cells.
 
Materials and Methods
Throughout this experimental study, NALM-6 cells were treated with different concentrations of telomerase inhibitor, MST-312 at different times. Then, cell viability and metabolic activity were evaluated by trypan blue and MTT assays; cell apoptosis was also evaluated by flow cytometry using Annexin V Apoptosis Detection Kit. In addition, the expression of BAX and BCL2 genes was evaluated in the treated cells using Quantitative Real-time PCR.
 
Results
A dose-and time-dependent decrease was observed in the viability of NALM-6 cells after exposure with different concentration of MST-312. Over 50% decrease was observed in the viability of the cells treated with 8 μM of MST-312 after 48 h. The cytotoxic effect of MST-312 was dose- dependent, with approximately 6, 19.69 and 56.9% reduction in metabolic activity of NALM-6 cells after 48 h exposure with 2, 4, and 8 μM of MST-312, respectively. Approximately 20% apoptosis was observed in NALM-6 cells treated with 4μM of MST-312 after 48 h.  Gene expression analysis also showed that 4μM of MST-312 led to upregulation of BAX and downregulation of Bcl-2 genes.
 
Conclusions 
Inhibition of telomerase activity by MST-312 can be proposed as a new candidate for the treatment of acute lymphoblastic leukemia.
 
Key words: Telomerase, Apoptosis, Acute Lymphoid Leukemia
 
 
 
 
 
Received:  8 Apr 2018
Accepted: 9 May 2018
 
 

Correspondence: Fatemi A., PhD of Hematology & Blood Banking. Assistant Professor of Department of Hematology and Medical Laboratory Sciences, Faculty of Allied Medical Sciences, Kerman University of Medical Sciences.
                Postal Code: 7619794435, Kerman, Iran. Tel: (+9834) 32112007; Fax: (+9834) 31325375
E-mail:
ahmad.fatemi2@gmail.com
Send email to the article author

Add your comments about this article
Your username or Email:

CAPTCHA


XML   Persian Abstract   Print


Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Ghasemimehr N, Yazdani Z, Farsinejad A, Mirzaee Khalilabadi R, Fatemi A. The effect of telomerase inhibitor MST-312 on apoptosis of acute lymphoblastic leukemia cell line NALM-6. Sci J Iran Blood Transfus Organ 2018; 15 (2) :120-132
URL: http://bloodjournal.ir/article-1-1195-en.html


Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Volume 15, Issue 2 (Summer 2018) Back to browse issues page
فصلنامه پژوهشی خون Scientific Journal of Iran Blood Transfus Organ
The Scientific Journal of Iranian Blood Transfusion Organization - Copyright 2006 by IBTO
Persian site map - English site map - Created in 0.06 seconds with 39 queries by YEKTAWEB 4645