title: Gracilaria edulis extract induces apoptosis and inhibits tumor in Ehrlich ascites tumor cells in vivo.
abstract: BACKGROUND
  Marine environment is inestimable for their chemical and biological diversity and therefore is an extraordinary resource for the discovery of new anticancer drugs. Recent development in elucidation of the mechanism and therapeutic action of natural products helped to evaluate for their potential activity.
  
  
  METHODS
  We evaluated Gracilaria edulis J. Ag (Brown algae), for its antitumor potential against the Ehrlich ascites tumor (EAT) in vivo and in vitro. Cytotoxicity evaluation of Ethanol Extract of Gracilaria edulis (EEGE) using EAT cells showed significant activity. In vitro studies indicated that EEGE cytotoxicity to EAT cells is mediated through its ability to produce reactive oxygen species (ROS) and therefore decreasing intracellular glutathione (GSH) levels may be attributed to oxidative stress.
  
  
  RESULTS
  Apoptotic parameters including Annexin-V positive cells, increased levels of DNA fragmentation and increased caspase-2, caspase-3 and caspase-9 activities indicated the mechanism might be by inducing apoptosis. Intraperitoneally administration of EEGE to EAT-bearing mice helped to increase the lifespan of the animals significantly inhibited tumor growth and increased survival of mice. Extensive hematology, biochemistry and histopathological analysis of liver and kidney indicated that daily doses of EEGE up to 300 mg/kg for 35 days are well tolerated and did not cause hematotoxicity nor renal or hepatotoxicity.
  
  
  CONCLUSIONS
  Comprehensive antitumor analysis in animal model and in Ehrlich Ascites Tumor cells was done including biochemical, and pathological evaluations indicate antitumor activity of the extract and non toxic in vivo. It was evident that the mechanism explains the apoptotic activity of the algae extract.
authors.affiliation: Medical University of the Americas, Charlestown, Nevis, West Indies. s.patra@mua.edu.
authors.forename: Satyajit
authors.initials: S
authors.lastname: Patra
authors.forename: Meenakshi Sundaram
authors.initials: MS
authors.lastname: Muthuraman
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001835:Body Weight; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D044724:Gracilaria / Q000737:chemistry*; D007668:Kidney / Q000737:chemistry / Q000187:drug effects; D008099:Liver / Q000737:chemistry / Q000187:drug effects; D051379:Mice; D010936:Plant Extracts / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D018709:Statistics, Nonparametric; D014407:Tumor Cells, Cultured
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D005978:Glutathione