Tags

Type your tag names separated by a space and hit enter

c-Myc Inhibition Using 10058-F4 Increased the Sensitivity of Acute Promyelocytic Leukemia Cells to Arsenic Trioxide Via Blunting PI3K/NF-κB Axis.
Arch Med Res. 2020 Jun 14 [Online ahead of print]AM

Abstract

BACKGROUNDS

Although ATO is widely used to treat acute promelocytic leukemia (APL), the appropriate effects of the drug as a single agent are achieved in high doses which are not clinically achievable without the risk of side effects; highlighting the necessity of its application in a combined-modality. Herein, we aimed to investigate whether c-Myc inhibition could reinforce the anti-leukemic effect of ATO, while reducing its concentration in APL cells.

METHODS

NB4 cells were treated with the relevant concentrations of 10058-F4 (c-Myc inhibitor) and ATO, and then the survival of the cells was evaluated using trypan blue, MTT and BrdU assays. Moreover, the mechanism of action of the agents were evaluated using Flow cytometry, qRT-PCR and western blot analysis.

RESULTS

We found that the inhibition of c-Myc using 10058-F4 could enhance the anti-leukemic effect of ATO in APL cells through reducing the phosphorylation of IκB, decreasing the expression of the anti-apoptotic genes and in turn, inducing a caspase-3-dependent apoptotic cell death. Moreover, the combination of 10058-F4 and ATO abrogated the activation of the PI3K pathway, while neither agent had significant suppressive impact on this pathway; suggesting for the first time that probably the companionship of c-Myc inhibitor may be an appealing strategy for shifting the resistance condition toward a chemo-sensitive phenotype, without the necessity to elevate the effective dose of ATO.

CONCLUSION

Given the efficacy of 10058-F4 in adjuvanting approaches, we suggest this small molecule inhibitor as an impressing agent to be used alongside ATO in the treatment of APL.

Authors+Show Affiliations

Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran; School of Allied Medical Sciences, Arak University of Medical Sciences, Arak, Iran.Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.Pediatric Congenital Hematologic Disorders Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.Department of Internal Medicine, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: d.bashash@sbmu.ac.ir.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32553459

Citation

Sayyadi, Mohammad, et al. "C-Myc Inhibition Using 10058-F4 Increased the Sensitivity of Acute Promyelocytic Leukemia Cells to Arsenic Trioxide Via Blunting PI3K/NF-κB Axis." Archives of Medical Research, 2020.
Sayyadi M, Safaroghli-Azar A, Pourbagheri-Sigaroodi A, et al. C-Myc Inhibition Using 10058-F4 Increased the Sensitivity of Acute Promyelocytic Leukemia Cells to Arsenic Trioxide Via Blunting PI3K/NF-κB Axis. Arch Med Res. 2020.
Sayyadi, M., Safaroghli-Azar, A., Pourbagheri-Sigaroodi, A., Abolghasemi, H., Anoushirvani, A. A., & Bashash, D. (2020). C-Myc Inhibition Using 10058-F4 Increased the Sensitivity of Acute Promyelocytic Leukemia Cells to Arsenic Trioxide Via Blunting PI3K/NF-κB Axis. Archives of Medical Research. https://doi.org/10.1016/j.arcmed.2020.06.002
Sayyadi M, et al. C-Myc Inhibition Using 10058-F4 Increased the Sensitivity of Acute Promyelocytic Leukemia Cells to Arsenic Trioxide Via Blunting PI3K/NF-κB Axis. Arch Med Res. 2020 Jun 14; PubMed PMID: 32553459.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - c-Myc Inhibition Using 10058-F4 Increased the Sensitivity of Acute Promyelocytic Leukemia Cells to Arsenic Trioxide Via Blunting PI3K/NF-κB Axis. AU - Sayyadi,Mohammad, AU - Safaroghli-Azar,Ava, AU - Pourbagheri-Sigaroodi,Atieh, AU - Abolghasemi,Hassan, AU - Anoushirvani,Ali Arash, AU - Bashash,Davood, Y1 - 2020/06/14/ PY - 2019/11/28/received PY - 2020/04/03/revised PY - 2020/06/03/accepted PY - 2020/6/20/entrez KW - 10058-F4 KW - Acute promyelocytic leukemia (APL) KW - Arsenic trioxide (ATO) KW - NF-κB KW - PI3K KW - c-Myc JF - Archives of medical research JO - Arch. Med. Res. N2 - BACKGROUNDS: Although ATO is widely used to treat acute promelocytic leukemia (APL), the appropriate effects of the drug as a single agent are achieved in high doses which are not clinically achievable without the risk of side effects; highlighting the necessity of its application in a combined-modality. Herein, we aimed to investigate whether c-Myc inhibition could reinforce the anti-leukemic effect of ATO, while reducing its concentration in APL cells. METHODS: NB4 cells were treated with the relevant concentrations of 10058-F4 (c-Myc inhibitor) and ATO, and then the survival of the cells was evaluated using trypan blue, MTT and BrdU assays. Moreover, the mechanism of action of the agents were evaluated using Flow cytometry, qRT-PCR and western blot analysis. RESULTS: We found that the inhibition of c-Myc using 10058-F4 could enhance the anti-leukemic effect of ATO in APL cells through reducing the phosphorylation of IκB, decreasing the expression of the anti-apoptotic genes and in turn, inducing a caspase-3-dependent apoptotic cell death. Moreover, the combination of 10058-F4 and ATO abrogated the activation of the PI3K pathway, while neither agent had significant suppressive impact on this pathway; suggesting for the first time that probably the companionship of c-Myc inhibitor may be an appealing strategy for shifting the resistance condition toward a chemo-sensitive phenotype, without the necessity to elevate the effective dose of ATO. CONCLUSION: Given the efficacy of 10058-F4 in adjuvanting approaches, we suggest this small molecule inhibitor as an impressing agent to be used alongside ATO in the treatment of APL. SN - 1873-5487 UR - https://www.unboundmedicine.com/medline/citation/32553459/c-Myc_Inhibition_Using_10058-F4_Increased_the_Sensitivity_of_Acute_Promyelocytic_Leukemia_Cells_to_Arsenic_Trioxide_Via_Blunting_PI3K/NF-κB_Axis L2 - https://linkinghub.elsevier.com/retrieve/pii/S0188-4409(19)31228-7 DB - PRIME DP - Unbound Medicine ER -
Try the Free App:
Prime PubMed app for iOS iPhone iPad
Prime PubMed app for Android
Prime PubMed is provided
free to individuals by:
Unbound Medicine.