Targeting the mitochondrial apoptosis pathway by a newly synthesized COX-2 inhibitor in pediatric ALL lymphocytes

Author:

Aghvami Marjan1,Salimi Ahmad2,Eshghi Peyman3,Zarei Mohammad H1,Farzaneh Shabnam1,Sattari Fatemeh1,Zarghi Afshin1,Pourahmad Jalal1

Affiliation:

1. Department of Pharmacology & Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, 1991953381, Iran

2. Department of Pharmacology & Toxicology, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran

3. Pediatric Congenital Hematologic Disorders Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Abstract

Aim: Acute lymphoblastic leukemia (ALL) is known as a barely curable malignancy. Particular mutations involved in apoptosis may have a main role in the onset of ALL in the pediatric patients. It has been proven that cycloxygenase-2 is capable of impairing the apoptosis pathway through mitochondria in tumor cells. Methodology: In this study, we investigated selective toxicity of a newly synthesized chalconeferrocenyl derivative as a selective cycloxygenase-2 inhibitor in ALL and healthy B-lymphocytes, and also isolated mitochondria obtained from them. For this purpose, we evaluated the cellar parameters like viability, apoptosis/necrosis, caspase-3 activation and ATP content, and also mitochondrial parameters like mitochondrial membrane potential decline, reactive oxygen species formation, cytochrome C release and mitochondrial swelling. Conclusion: Our results implied that this compound can selectively induce cellular and mitochondrial toxicity in cancerous ALL B-lymphocytes and obtained mitochondria from them without any detrimental effects on healthy subjects.

Publisher

Future Science Ltd

Subject

Drug Discovery,Pharmacology,Molecular Medicine

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