Novel bioactive hybrid Celecoxib-HDAC Inhibitor, induces apoptosis in human acute lymphoblastic leukemia cells

Jing Liu; Li Zhang; Ling Guo; Yan Zeng; Qulian Guo; Chunmei Yang; Jian Shu; Wenjun Liu; Lu Yang

doi:10.1016/j.bmc.2022.117085

Novel bioactive hybrid Celecoxib-HDAC Inhibitor, induces apoptosis in human acute lymphoblastic leukemia cells

Bioorg Med Chem. 2022 Dec 1:75:117085. doi: 10.1016/j.bmc.2022.117085. Epub 2022 Nov 5.

Authors

Jing Liu¹, Li Zhang¹, Ling Guo¹, Yan Zeng¹, Qulian Guo¹, Chunmei Yang², Jian Shu², Wenjun Liu³, Lu Yang⁴

Affiliations

¹ Department of Pediatrics, Children Hematological Oncology and Birth Defects Laboratory, The Affiliated Hospital of Southwest Medical University, Sichuan Clinical Research Center for Birth Defects, Luzhou, Sichuan 646000, China.
² Department of Radiology, The Affiliated Hospital of Southwest Medical University, Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou 646000, China.
³ Department of Pediatrics, Children Hematological Oncology and Birth Defects Laboratory, The Affiliated Hospital of Southwest Medical University, Sichuan Clinical Research Center for Birth Defects, Luzhou, Sichuan 646000, China. Electronic address: wenjun_liu@swmu.edu.cn.
⁴ Department of Radiology, The Affiliated Hospital of Southwest Medical University, Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou 646000, China. Electronic address: yanglu@swmu.edu.cn.

PMID: 36395680
DOI: 10.1016/j.bmc.2022.117085

Abstract

Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Here, we exploited the synergy between histone deacetylase inhibitors (HDACi) and cyclooxygenase 2 (COX-2) inhibitors by generating and testing a series of hybrid Celecoxib-HDAC inhibitors (selenium-containing analogues of Celecoxib) on ALL cells, of which compound 11 exhibited significant inducement to kill NALM6 cells with an average IC₅₀ of 9.95 ± 0.44 μM compared with control Celecoxib at 28.58 ± 1.44 μM and inhibited NALM6 cells growth via the inhibition of the cell cycle in G2 phase. Furthermore, compound 11 induced apoptosis by activating PARP cleavage. Taken together, compound 11 possessed the potential to be developed further as a chemotherapeutic agent for ALL.

Keywords: ALL; Apoptosis; Celecoxib derivatives; Dual inhibitor; HDACi.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis
Celecoxib / pharmacology
Cell Line, Tumor
Child
Cyclooxygenase 2 Inhibitors / pharmacology
Cyclooxygenase 2 Inhibitors / therapeutic use
Histone Deacetylase Inhibitors* / pharmacology
Humans
Precursor Cell Lymphoblastic Leukemia-Lymphoma* / drug therapy

Substances

Celecoxib
Histone Deacetylase Inhibitors
Cyclooxygenase 2 Inhibitors