Logo Medical Science Monitor

Call: +1.631.470.9640
Mon - Fri 10:00 am - 02:00 pm EST

Contact Us

Logo Medical Science Monitor Logo Medical Science Monitor Logo Medical Science Monitor

08 April 2020 : Laboratory Research  

Bromodomains and Extra-Terminal (BET) Inhibitor JQ1 Suppresses Proliferation of Acute Lymphocytic Leukemia by Inhibiting c-Myc-Mediated Glycolysis

Meng-Yi Zhang12ABCDEF, Sheng-Li Liu1ACE, Wen-Li Huang3BC, Da-Bin Tang1BC, Wei-Wei Zheng1BC, Neng Zhou1BC, Hang Zhou1BC, Tuersunayi Abudureheman1BC, Zhong-Hua Tang1D, Bin-Bing S. Zhou12ACEG, Cai-Wen Duan12ACEG*

DOI: 10.12659/MSM.923411

Med Sci Monit 2020; 26:e923411

Abstract

BACKGROUND: Acute lymphocytic leukemia (ALL) is a common blood cancer which induces high mortality in children. Bromodomains and extra-terminal (BET) protein inhibitors, such as JQ1 and ARV-825, are promising cancer therapeutic agents that can be used by targeting c-Myc. A recent work reported that JQ1 effectively attenuates ALL in vitro by suppressing cell proliferation and accelerating apoptosis. The purpose of this research was to probe into the potential mechanism of how JQ1 inhibits ALL cell proliferation in vitro.

MATERIAL AND METHODS: Cell viability of ALL cells were measured by CTG after treatment by JQ1. Cell cycle analysis was done by EdU and PI staining. Cell apoptosis was assessed by Annexin V/PI staining. Glycolysis was detected using Seahorse and LC-MS kits. The expression of glycolytic rate-limiting enzymes was assessed by RNA-seq, qRT-PCR, and Western blot.

RESULTS: JQ1 suppressed cell proliferation by arresting the cell cycle and inducing the apoptosis of acute lymphocytic leukemia cells. JQ1 inhibited cell proliferation of B-ALL cells by restraining glycolysis. Conversely, the cell cycle block of B-ALL cells induced by JQ1 was partially abolished after pretreatment with 2-Deoxy-D-glucose (2-DG), an inhibitor of glycolysis. Furthermore, JQ1 restrained the glycolysis of B-ALL cell lines by remarkably downregulating the rate-limiting enzymes of glycolysis, such as hexokinase 2, phosphofructokinase, and lactate dehydrogenase A. Moreover, the cell cycle arrest was reversed in B-ALL cells with overexpressed c-Myc treated by JQ1, which is involved in the enhancement of glycolysis.

CONCLUSIONS: The BET inhibitor JQ1 suppresses the proliferation of ALL by inhibiting c-Myc-mediated glycolysis, thus providing a new strategy for the treatment of ALL.

Keywords: Cell Cycle, Genes, myc, Glycolysis, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Azepines, Cell Cycle Checkpoints, Cell Cycle Proteins, HEK293 Cells, Nuclear Proteins, Proteins, Proto-Oncogene Proteins c-myc, Transcription Factors, Triazoles

Add Comment 0 Comments

Editorial

01 April 2024 : Editorial  

Editorial: Forty Years of Waiting for Prevention and Cure of HIV Infection – Ongoing Challenges and Hopes for Vaccine Development and Overcoming Antiretroviral Drug Resistance

Dinah V. Parums

DOI: 10.12659/MSM.944600

Med Sci Monit 2024; 30:e944600

0:00

In Press

05 Apr 2024 : Clinical Research  

Comparative Analysis of Transoral Endoscopic Parathyroidectomy Vestibular Approach and Focused Open Surgery...

Med Sci Monit In Press; DOI: 10.12659/MSM.944128  

05 Mar 2024 : Clinical Research  

Muscular Function Recovery from General Anesthesia in 132 Patients Undergoing Surgery with Acceleromyograph...

Med Sci Monit In Press; DOI: 10.12659/MSM.942780  

05 Mar 2024 : Clinical Research  

Effects of Thermal Insulation on Recovery and Comfort of Patients Undergoing Holmium Laser Lithotripsy

Med Sci Monit In Press; DOI: 10.12659/MSM.942836  

05 Mar 2024 : Clinical Research  

Role of Critical Shoulder Angle in Degenerative Type Rotator Cuff Tears: A Turkish Cohort Study

Med Sci Monit In Press; DOI: 10.12659/MSM.943703  

Most Viewed Current Articles

17 Jan 2024 : Review article  

Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron Variant

DOI :10.12659/MSM.942799

Med Sci Monit 2024; 30:e942799

0:00

14 Dec 2022 : Clinical Research  

Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase Levels

DOI :10.12659/MSM.937990

Med Sci Monit 2022; 28:e937990

0:00

16 May 2023 : Clinical Research  

Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...

DOI :10.12659/MSM.940387

Med Sci Monit 2023; 29:e940387

0:00

01 Jan 2022 : Editorial  

Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...

DOI :10.12659/MSM.935952

Med Sci Monit 2022; 28:e935952

0:00

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750