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

• Published in: Future medicinal chemistry Vol. 10; no. 19; pp. 2277 - 2289
• Main Authors: Aghvami, Marjan, Salimi, Ahmad, Eshghi, Peyman, Zarei, Mohammad H, Farzaneh, Shabnam, Sattari, Fatemeh, Zarghi, Afshin, Pourahmad, Jalal
• Format: Journal Article
• Language: English
• Published: England Future Science Ltd 01.10.2018; 01.10.2018
• Subjects: Adenosine Triphosphate - metabolism; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; apoptosis; Apoptosis - drug effects; B-Lymphocytes - cytology; B-Lymphocytes - drug effects; B-Lymphocytes - metabolism; Caspase 3 - metabolism; Cell Survival - drug effects; Child; Child, Preschool; Cyclooxygenase 2 Inhibitors - chemical synthesis; Cyclooxygenase 2 Inhibitors - pharmacology; Cyclooxygenase 2 Inhibitors - therapeutic use; cyclooxygenase-2 selective inhibitors; Female; Humans; Male; Membrane Potential, Mitochondrial - drug effects; mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; pediatric ALL; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology; Reactive Oxygen Species - metabolism; cyclooxygenase-2 selective inhibitors; apoptosis; pediatric ALL; mitochondria
• ISSN: 1756-8919; 1756-8927; 1756-8927
• DOI: 10.4155/fmc-2018-0032

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. 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. 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.