CYTOTOXIC EFFECT OF TELOMERASE CATALYTIC (HTERT) AND NUCLEOTIDE (HTERC) SUBUNIT INHIBITORS ON ACUTE PROMYELOCYTIC LEUKEMIA CELLS

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POURBAGHERI SIGAROODI ATIEH; Safaroghli Azar Ava; NEMATI MANSOOR FAHIMEH; BASHASH DAVOOD

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Paper Information

Journal: JOURNAL OF MAZANDARAN UNIVERSITY OF MEDICAL SCIENCES Year:2018 | Volume:28 | Issue:166 Page(s): 10-20

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Title

CYTOTOXIC EFFECT OF TELOMERASE CATALYTIC (HTERT) AND NUCLEOTIDE (HTERC) SUBUNIT INHIBITORS ON ACUTE PROMYELOCYTIC LEUKEMIA CELLS

Author(s)

POURBAGHERI SIGAROODI ATIEH | Safaroghli Azar Ava | NEMATI MANSOOR FAHIMEH | BASHASH DAVOOD | Issue Writer Certificate

Keywords

ACUTE PROMYELOCYTIC LEUKEMIAQ2

APOPTOSISQ1

NB4 CELLSQ2

TELOMERASEQ2

Abstract

Background and purpose: TELOMERASE activity has a major role in ACUTE PROMYELOCYTIC LEUKEMIA (APL). It also has a critical role in disease recurrence. This research aimed at studying the cytotoxic effects of TELOMERASE inhibition using oligonucleotide-based molecule against human TELOMERASE RNA template (hTERC antisense) and non-nucleoside small molecule targeting catalytic subunit (BIBR5132) on APL-derived cell line. Materials and methods: To evaluate whether inhibition of TELOMERASE using either hTERC antisense or BIBR5132 could exert cytotoxic effect in APL, NB4 CELLS were subjected to different concentrations of the inhibitors and subsequent cell viability, metabolic activity, induction of APOPTOSIS were investigated using Trypan blue assay, MTT, and annexin/PI staining, respectively. Also, Caspase-3 enzymatic activity and transcriptional alteration of APOPTOSIS-related target genes were investigated. Results: We found that targeting TELOMERASE using hTERC antisense (45 pmol/L) and BIBR1532 (75 µ L) for 48 h reduced the survival rate of NB4 CELLS nearly by 30% and 40%, respectively and induced a caspase-3-dependent APOPTOSIS. Our results also suggest that suppression of c-Myc and subsequent increment of Bax/Bcl-2 ratio coupled with decreased TELOMERASE activity may be rational mechanisms for the cytotoxicity of both TELOMERASE inhibitors against NB4 CELLS. Conclusion: Current results clearly indicated that both BIBR1532 and hTERC antisense had anti-tumor activity against NB4 CELLS and anti-telomerase-based therapy may be an efficient treatment for ACUTE PROMYELOCYTIC LEUKEMIA.

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APA: Copy

POURBAGHERI SIGAROODI, ATIEH, Safaroghli Azar, Ava, NEMATI MANSOOR, FAHIMEH, & BASHASH, DAVOOD. (2018). CYTOTOXIC EFFECT OF TELOMERASE CATALYTIC (HTERT) AND NUCLEOTIDE (HTERC) SUBUNIT INHIBITORS ON ACUTE PROMYELOCYTIC LEUKEMIA CELLS. JOURNAL OF MAZANDARAN UNIVERSITY OF MEDICAL SCIENCES, 28(166 ), 10-20. SID. https://sid.ir/paper/44568/en

Vancouver: Copy

POURBAGHERI SIGAROODI ATIEH, Safaroghli Azar Ava, NEMATI MANSOOR FAHIMEH, BASHASH DAVOOD. CYTOTOXIC EFFECT OF TELOMERASE CATALYTIC (HTERT) AND NUCLEOTIDE (HTERC) SUBUNIT INHIBITORS ON ACUTE PROMYELOCYTIC LEUKEMIA CELLS. JOURNAL OF MAZANDARAN UNIVERSITY OF MEDICAL SCIENCES[Internet]. 2018;28(166 ):10-20. Available from: https://sid.ir/paper/44568/en

IEEE: Copy

ATIEH POURBAGHERI SIGAROODI, Ava Safaroghli Azar, FAHIMEH NEMATI MANSOOR, and DAVOOD BASHASH, “CYTOTOXIC EFFECT OF TELOMERASE CATALYTIC (HTERT) AND NUCLEOTIDE (HTERC) SUBUNIT INHIBITORS ON ACUTE PROMYELOCYTIC LEUKEMIA CELLS,” JOURNAL OF MAZANDARAN UNIVERSITY OF MEDICAL SCIENCES, vol. 28, no. 166 , pp. 10–20, 2018, [Online]. Available: https://sid.ir/paper/44568/en

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