title: Ellagic acid, a polyphenolic compound, selectively induces ROS-mediated apoptosis in cancerous B-lymphocytes of CLL patients by directly targeting mitochondria.
abstract: To investigate the effects ofellagic acid (EA) on the cytotoxicity, B-lymphocytes isolated from CLL patients and healthy individuals. Flow cytometric assay was used to measure the percentage of apoptosis versus necrosis, intracellular active oxygen radicals (ROS), mitochondrial membrane potential (MMP) and the caspase-3 activity and then mitochondria were isolated from both groups B-lymphocytes and parameters of mitochondrial toxicity was investigated. Based on our results EA decreased the percentage of viable cells and induced apoptosis. EA increased ROS formation, mitochondria swelling, MMP decrease and cytochrome c release in mitochondria isolated from CLL BUT NOT healthy B-lymphocytes while pre-treatment with cyclosporine A and Butylated hydroxyl toluene (BHT) prevented these effects. Our results suggest that EA can act as an anti cancer candidate by directly and selectively targeting mitochondria could induce apoptosis through mitochondria pathway with increasing ROS production which finally ends in cytochrome c release, caspase 3 activation and apoptosis in cancerous B-lymphocytes isolated from CLL patients.
authors.affiliation: Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Salimi
authors.affiliation: Iranian Blood Transfusion Organization, Tehran, Iran.
authors.forename: Mehryar Habibi
authors.initials: MH
authors.lastname: Roudkenar
authors.affiliation: Shohadaye Tajrish Educational Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Leila
authors.initials: L
authors.lastname: Sadeghi
authors.affiliation: Iranian Blood Transfusion Organization, Tehran, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Mohseni
authors.affiliation: Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Enayatollah
authors.initials: E
authors.lastname: Seydi
authors.affiliation: Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Pharmacology, Shiraz University, Shiraz, Iran.
authors.forename: Nahal
authors.initials: N
authors.lastname: Pirahmadi
authors.affiliation: Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: j.pourahmadjaktaji@utoronto.ca.
authors.forename: Jalal
authors.initials: J
authors.lastname: Pourahmad
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001402:B-Lymphocytes / Q000187:drug effects / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D004610:Ellagic Acid / Q000494:pharmacology*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000473:pathology; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D008933:Mitochondrial Swelling; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D004610:Ellagic Acid; D045304:Cytochromes c; C505407:CASP3 protein, human; D053148:Caspase 3
keywords: Active oxygen radicals (ROS); Apoptosis; Chronic lymphocytic leukemia (CLL); Ellagic acid; Mitochondria