title: Selective toxicity of persian gulf sea cucumber holothuria parva on human chronic lymphocytic leukemia b lymphocytes by direct mitochondrial targeting.
abstract: Natural products isolated from marine environment are well known for their pharmacodynamic potential in diversity of disease treatments such as cancer or inflammatory conditions. Sea cucumbers are one of the marine animals of the phylum Echinoderm. Many studies have shown that the sea cucumber contains antioxidants and anti-cancer compounds. Chronic lymphocytic leukemia (CLL) is a disease characterized by the relentless accumulation of CD5+B lymphocytes. CLL is the most common leukemia in adults, about 25-30% of all leukemias. In this study B lymphocytes and their mitochondria (cancerous and non-cancerous) were obtained from peripheral blood of human subjects and B lymphocyte cytotoxicity assay, and caspase 3 activation along with mitochondrial upstream events of apoptosis signaling including reactive oxygen species (ROS) production, collapse of mitochondrial membrane potential (MMP) and mitochondrial swelling were determined following the addition of Holothuria parva extract to both cancerous and non-cancerous B lymphocytes and their mitochondria. Our in vitro finding showed that mitochondrial ROS formation, MMP collapse, and mitochondrial swelling and cytochrome c release were significantly (P < 0.05) increased after addition of different concentrations of H. parva only in cancerous BUT NOT normal non-cancerous mitochondria. Consistently, different concentrations of H. parva significantly (P < 0.05) increased cytotoxicity and caspase 3 activation only in cancerous BUT NOT normal non-cancerous B lymphocytes. These results showed that H. parva methanolic extract has a selective mitochondria mediated apoptotic effect on chronic lymphocytic leukemia B lymphocytes hence may be promising in the future anticancer drug development for treatment of CLL. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1158-1169, 2017.
authors.affiliation: Department of Pharmacology and Toxicology Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.|Department of Pharmacology and Toxicology School of Pharmacy, Ardabil University of Medical Science, Ardabil, Iran.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Salimi
authors.affiliation: Ministry of Jihad-e-Agriculture, Research and Education and Extension Organization (AREEO) and Iranian Fisheries Research Organization, Tehran, Iran.
authors.forename: Abbasali
authors.initials: A
authors.lastname: Motallebi
authors.affiliation: Department of Pharmacology and Toxicology Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Ayatollahi
authors.affiliation: Department of Pharmacology and Toxicology Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Enayatollah
authors.initials: E
authors.lastname: Seydi
authors.affiliation: Department of Laboratory Sciences Faculty of Paramedicine, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Ali Reza
authors.initials: AR
authors.lastname: Mohseni
authors.affiliation: Education and Extension Organization (AREEO), Iranian Fisheries Research Institute, Persian Gulf and Oman Sea Ecological Research Agricultural Research, Bandar Abbas, Iran.
authors.forename: Melika
authors.initials: M
authors.lastname: Nazemi
authors.affiliation: Department of Pharmacology and Toxicology Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.|Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Jalal
authors.initials: J
authors.lastname: Pourahmad
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001402:B-Lymphocytes / Q000187:drug effects* / Q000502:physiology; D016022:Case-Control Studies; D002470:Cell Survival; D045304:Cytochromes c / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D005260:Female; D047332:Holothuria / Q000737:chemistry*; D006801:Humans; D019156:Indian Ocean; D007938:Leukemia / Q000188:drug therapy; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008933:Mitochondrial Swelling / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D045304:Cytochromes c
keywords: B lymphocyte; Holothuria parva; chronic lymphocytic leukemia; isolated mitochondria; sea cucumber