title: Selective Toxicity of Persian Gulf Sea Cucumber (Holothuria parva) and Sponge (Haliclona oculata) Methanolic Extracts on Liver Mitochondria Isolated from an Animal Model of Hepatocellular Carcinoma.
abstract: BACKGROUND
  Natural products isolated from marine environments are well known for their pharmacodynamic potential in diverse disease treatments, such as for cancer or inflammatory conditions. Sea cucumbers are marine animals of the phylum Echinoderm and the class Holothuroidea, with leathery skin and gelatinous bodies. Sponges are important components of Persian Gulf animal communities, and the marine sponges of the genus Haliclona have been known to display broad-spectrum biological activity. Many studies have shown that sea cucumbers and sponges contain antioxidants and anti-cancer compounds.
  
  
  OBJECTIVE
  This study was designed to determine the selective toxicity of Persian Gulf sea cucumber (Holothuria parva) and sponge (Haliclona oculata) methanolic extracts on liver mitochondria isolated from an animal model of hepatocellular carcinoma, as part of a national project that hopes to identify novel potential anticancer candidates among Iranian Persian Gulf flora and fauna.
  
  
  METHODS
  To induce hepatocarcinogenesis, rats were given diethylnitrosamine (DEN) injections (200 mg/kg i.p. by a single dose), and then the cancer was promoted with 2-acetylaminofluorene (2-AAF) (0.02 w/w) for two weeks. Histopathological evaluations were performed, and levels of liver injury markers and a specific liver cancer marker (alpha-fetoprotein), were determined for confirmation of hepatocellular carcinoma induction. Finally, mitochondria were isolated from cancerous and non-cancerous hepatocytes.
  
  
  RESULTS
  Our results showed that H. parva methanolic extracts (250, 500, and 1000 µg/mL) and H. oculata methanolic extracts (200, 400, and 800 µg/mL) increased reactive oxygen species (ROS) formation, mitochondrial membrane potential (MMP), mitochondrial swelling, and cytochrome c release in the mitochondria obtained from cancerous hepatocytes, but not in mitochondria obtained from non-cancerous liver hepatocytes. These extracts also induced caspase-3 activation, which is known as a final mediator of apoptosis, in the hepatocytes obtained only from cancerous, not non-cancerous, rat livers.
  
  
  CONCLUSIONS
  Our results suggest that H. parva and H. oculata may be promising therapeutic candidates for the treatment of HCC, following further confirmatory in vivo experiments and clinical trials.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.
authors.forename: Enayatollah
authors.initials: E
authors.lastname: Seydi
authors.affiliation: Research and Education and Extension Organization (AREEO) and Iranian Fisheries Research Organization, Ministry of Jihad-e-Agriculture, Tehran, IR 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, IR Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Dastbaz
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.
authors.forename: Sahar
authors.initials: S
authors.lastname: Dehghan
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran; Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, IR Iran.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Salimi
authors.affiliation: Research and Education and Extension Organization (AREEO) and Iranian Fisheries Research Organization, Ministry of Jihad-e-Agriculture, Tehran, IR 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, IR Iran.
authors.forename: Jalal
authors.initials: J
authors.lastname: Pourahmad
keywords: Carcinoma, Hepatocellular; Haliclona oculata; Hepatocytes; Holothuria parva; Mitochondria