Research Article For reprint orders, please contact: reprints@future-science.com Targeting the mitochondrial apoptosis pathway by a newly synthesized COX-2 inhibitor in pediatric ALL lymphocytes Marjan Aghvami ‡,1 , Ahmad Salimi ‡,2 , Peyman Eshghi 3 , Mohammad H Zarei 1 , Shabnam Farzaneh 1 , Fatemeh Sattari 1 , Afshin Zarghi** ,1 & Jalal Pourahmad* ,1 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 *Author for correspondence: j.pourahmadjaktaji@utoronto.ca **Author for correspondence: zarghi@sbmu.ac.ir ‡ Authors contributed equally 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 mito- chondrial membrane potential decline, reactive oxygen species formation, cytochrome C release and mito- chondrial 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. In the ALL cells Caspase 3 Caspase 9 Apoptosome Apaf-1 Pro-caspase 9 Cytochrome C MPT pore opening OM IMS IM Matrix COX 2 Cytochrome C Apoptosis • ROS formation • MMP decline • Mitochondrial swelling • ATP deplete Fe O SO 2 M First draft submitted: 27 February 2018; Accepted for publication: 20 September 2018; Published online: 11 October 2018 Keywords: apoptosis • cyclooxygenase-2 selective inhibitors • mitochondria • pediatric ALL Future Med. Chem. (Epub ahead of print) ISSN 1756-8919 10.4155/fmc-2018-0032 C  2018 Newlands Press