Cytotoxic and Apoptotic Effects of C-Myc Inhibition by 10058-F4 on Acute Promyelocytic Leukemia Cells

BACKGROUND AND OBJECTIVE: C-Myc plays a very important role in controlling cell proliferation, apoptosis and differentiation. Due to the involvement of c-Myc in the regulation of a wide range of intracellular functions and based on its role in the pathogenesis of acute promyelocytic leukemia (APL),...

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Autores principales: M Sayyadi, A Safaroghli-Azar, D Bashash
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Publicado: Babol University of Medical Sciences 2021
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spelling oai:doaj.org-article:413408a6ed424f8989e2130e9548a7022021-11-29T07:40:49ZCytotoxic and Apoptotic Effects of C-Myc Inhibition by 10058-F4 on Acute Promyelocytic Leukemia Cells1561-41072251-7170https://doaj.org/article/413408a6ed424f8989e2130e9548a7022021-03-01T00:00:00Zhttp://jbums.org/article-1-9093-en.htmlhttps://doaj.org/toc/1561-4107https://doaj.org/toc/2251-7170BACKGROUND AND OBJECTIVE: C-Myc plays a very important role in controlling cell proliferation, apoptosis and differentiation. Due to the involvement of c-Myc in the regulation of a wide range of intracellular functions and based on its role in the pathogenesis of acute promyelocytic leukemia (APL), the present study was conducted to investigate the anti-leukemia effect of 10058-F4, as a known c-Myc inhibitor, on APL-derived HL-60 cells. METHODS: In this experimental study, to evaluate the cytotoxic effects of 10058-F4 in acute promyelocytic leukemia, HL-60 cell line (prepared from Pasteur Institute of Iran) was treated with different doses of inhibitor (50, 100, 150 and 200 μM) and then in 24 -and 36- hours intervals, survival rate, cell count, metabolic activity and induction of apoptosis were respectively evaluated. In addition, transcriptional changes of apoptosis-related genes were studied by real-time PCR to investigate the molecular mechanisms of function of 10058-F4. FINDINGS: The results showed that inhibition of c-Myc by 10058-F4 at doses of 150 and 200 μM in 24 hours reduced the growth of HL-60 cells by 38±4% and 49±3.2%, respectively, compared to the control group (p<0.05). In addition, the cytotoxic effects of the drug are due to the arrest of cells in the G1 phase and the induction of apoptosis; Because the percentage of cells stained with Annexin V/PI in cells treated at a dose of 100 μM after 24 hours increased by 31% compared to the control group (p<0.05). CONCLUSION: In this study, the efficacy of 10058-F4 in HL-60 cells was fully established.M SayyadiA Safaroghli-AzarD BashashBabol University of Medical Sciencesarticleacute promyelocytic leukemiac-myc10058-f4hl-60 cell line.MedicineRMedicine (General)R5-920ENFAMajallah-i Dānishgāh-i ̒Ulūm-i Pizishkī-i Bābul, Vol 23, Iss 1, Pp 150-157 (2021)
institution DOAJ
collection DOAJ
language EN
FA
topic acute promyelocytic leukemia
c-myc
10058-f4
hl-60 cell line.
Medicine
R
Medicine (General)
R5-920
spellingShingle acute promyelocytic leukemia
c-myc
10058-f4
hl-60 cell line.
Medicine
R
Medicine (General)
R5-920
M Sayyadi
A Safaroghli-Azar
D Bashash
Cytotoxic and Apoptotic Effects of C-Myc Inhibition by 10058-F4 on Acute Promyelocytic Leukemia Cells
description BACKGROUND AND OBJECTIVE: C-Myc plays a very important role in controlling cell proliferation, apoptosis and differentiation. Due to the involvement of c-Myc in the regulation of a wide range of intracellular functions and based on its role in the pathogenesis of acute promyelocytic leukemia (APL), the present study was conducted to investigate the anti-leukemia effect of 10058-F4, as a known c-Myc inhibitor, on APL-derived HL-60 cells. METHODS: In this experimental study, to evaluate the cytotoxic effects of 10058-F4 in acute promyelocytic leukemia, HL-60 cell line (prepared from Pasteur Institute of Iran) was treated with different doses of inhibitor (50, 100, 150 and 200 μM) and then in 24 -and 36- hours intervals, survival rate, cell count, metabolic activity and induction of apoptosis were respectively evaluated. In addition, transcriptional changes of apoptosis-related genes were studied by real-time PCR to investigate the molecular mechanisms of function of 10058-F4. FINDINGS: The results showed that inhibition of c-Myc by 10058-F4 at doses of 150 and 200 μM in 24 hours reduced the growth of HL-60 cells by 38±4% and 49±3.2%, respectively, compared to the control group (p<0.05). In addition, the cytotoxic effects of the drug are due to the arrest of cells in the G1 phase and the induction of apoptosis; Because the percentage of cells stained with Annexin V/PI in cells treated at a dose of 100 μM after 24 hours increased by 31% compared to the control group (p<0.05). CONCLUSION: In this study, the efficacy of 10058-F4 in HL-60 cells was fully established.
format article
author M Sayyadi
A Safaroghli-Azar
D Bashash
author_facet M Sayyadi
A Safaroghli-Azar
D Bashash
author_sort M Sayyadi
title Cytotoxic and Apoptotic Effects of C-Myc Inhibition by 10058-F4 on Acute Promyelocytic Leukemia Cells
title_short Cytotoxic and Apoptotic Effects of C-Myc Inhibition by 10058-F4 on Acute Promyelocytic Leukemia Cells
title_full Cytotoxic and Apoptotic Effects of C-Myc Inhibition by 10058-F4 on Acute Promyelocytic Leukemia Cells
title_fullStr Cytotoxic and Apoptotic Effects of C-Myc Inhibition by 10058-F4 on Acute Promyelocytic Leukemia Cells
title_full_unstemmed Cytotoxic and Apoptotic Effects of C-Myc Inhibition by 10058-F4 on Acute Promyelocytic Leukemia Cells
title_sort cytotoxic and apoptotic effects of c-myc inhibition by 10058-f4 on acute promyelocytic leukemia cells
publisher Babol University of Medical Sciences
publishDate 2021
url https://doaj.org/article/413408a6ed424f8989e2130e9548a702
work_keys_str_mv AT msayyadi cytotoxicandapoptoticeffectsofcmycinhibitionby10058f4onacutepromyelocyticleukemiacells
AT asafaroghliazar cytotoxicandapoptoticeffectsofcmycinhibitionby10058f4onacutepromyelocyticleukemiacells
AT dbashash cytotoxicandapoptoticeffectsofcmycinhibitionby10058f4onacutepromyelocyticleukemiacells
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