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

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.

A Newly Synthetized Ferrocenyl Derivative Selectively Induces Apoptosis in ALL Lymphocytes through Mitochondrial Estrogen Receptors.

BACKGROUND: Estrogens, as the main female steroid hormones have multiple proven effects on reproductive and non- reproductive systems. Expression of ERα and ERß, two dominant estrogen receptors, in peripheral blood mononuclear cells in certain B-cell malignancies and the existence of estrogens receptors on mitochondria is open to question that estrogen likely has an impact on the cancerous lymphocytes life span. Acute Lymphoblastic Leukemia (ALL) is the frequent pediatric malignity which is recurrent and hardly curable in many cases. The malignant cells are generally resistant to apoptosis caused the severe lymphocytes accumulation in the peripheral blood. METHODS: By focusing on mitochondria as a life/death center of the cell; in the current research we compared cytotoxicity effects of a new ferrocenyl derivative with raloxifene as well-known SERMs considering the apoptotic process and survival of cancerous lymphocytes. RESULTS: We demonstrated that both ferrocenyl derivative and raloxifene could cause mitochondrial lesion and initiate the apoptosis process by caspase activation and cytochrome c release. CONCLUSION: In brief, the ferrocenyl derivative could induce estrogen-related selective apoptosis on cancerous lymphocytes by affecting mitochondrial receptors.