title: In vivo antitumor effect, induction of apoptosis and safety of Remirea maritima Aubl. (Cyperaceae) extracts.
abstract: BACKGROUND
  Remirea maritima has been widely used in the treatment of diarrhea, kidney disease, and high fever and for therapeutic purposes, such as an analgesic and anti-inflammatory. However, few scientific research studies on its medicinal properties have been reported.
  
  
  OBJECTIVE
  The present study aimed to investigate the anticancer potential of aqueous extract (AE), 40% hydroalcoholic extracts (40HA) and 70% (70HA) from R. maritima in experimental models and to identify its phytochemical compounds.
  
  
  METHODS
  The chemical composition of AE, 40HA and 70HA was assessed by HPLC-DAD and ESI-IT-MS/MS. In vitro activity was determined on cultured tumor cell, NCI-H385N (Broncho-alveolar carcinoma), OVCAR-8 (Ovarian carcinoma) and PC-3M (prostate carcinoma) by the MTT assay, and the in vivo antitumor activity was assessed in Sarcoma 180-bearing mice. Toxicological parameters were also evaluated as well as the humoral immune response.
  
  
  RESULTS
  Among the aqueous and hydroalcoholic extracts of R. maritima, only 40HA showed in vitro biological effect potential, presenting IC50 values of 27.08, 46.62 and >50µg/ml for OVCAR-8, NCI-H385M and PC-3M cells lines, respectively. Regarding chemical composition, a mixture of isovitexin-2''-O-β-D-glucopyranoside, vitexin-2''-O-β-D-glucopyranoside, luteolin-7-O-glucuronide and 1-O-(E)-caffeoyl-β-D-glucose were identified as the major phytochemical compounds of the extracts. In the in vivo study, the tumor inhibition rates were 57.16-62.57% at doses of 25mg/kg and 50mg/kg, respectively, and the tumor morphology presented increasing numbers of apoptotic cells. Additionally, 40HA also demonstrated significantly increased of OVA-specific total Ig.
  
  
  CONCLUSIONS
  40HA exhibited in vitro and in vivo anticancer properties without substantial toxicity that could be associated with its immunostimulating properties.
authors.affiliation: Department of Pharmacy, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil.
authors.forename: Grace Anne A
authors.initials: GA
authors.lastname: Dória
authors.affiliation: Department of Pharmacy, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil.
authors.forename: Paula P
authors.initials: PP
authors.lastname: Menezes
authors.affiliation: Department of Pharmacy, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil.
authors.forename: Bruno S
authors.initials: BS
authors.lastname: Lima
authors.affiliation: Department of Pharmacy, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil.
authors.forename: Bruno S
authors.initials: BS
authors.lastname: Vasconcelos
authors.affiliation: Department of Pharmacy, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil.
authors.forename: Francilene A
authors.initials: FA
authors.lastname: Silva
authors.affiliation: Department of Physiology, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil.
authors.forename: Raíssa M
authors.initials: RM
authors.lastname: Henriques
authors.affiliation: Department of Pharmacy, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil.
authors.forename: Marcélia G D
authors.initials: MG
authors.lastname: Melo
authors.affiliation: Institute of Technology and Research, Tiradentes University, Aracaju, Sergipe, Brazil.
authors.forename: Ângela V F
authors.initials: ÂV
authors.lastname: Alves
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Manoel O
authors.initials: MO
authors.lastname: Moraes
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Cláudia Ó
authors.initials: CÓ
authors.lastname: Pessoa
authors.affiliation: Department of Physiology, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil.
authors.forename: Adriana A
authors.initials: AA
authors.lastname: Carvalho
authors.affiliation: Department of Biology, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil.
authors.forename: Ana Paula N
authors.initials: AP
authors.lastname: Prata
authors.affiliation: Institute of Technology and Research, Tiradentes University, Aracaju, Sergipe, Brazil.
authors.forename: Ricardo Luiz C A
authors.initials: RL
authors.lastname: Junior
authors.affiliation: Institute of Technology and Research, Tiradentes University, Aracaju, Sergipe, Brazil.
authors.forename: Isabel B
authors.initials: IB
authors.lastname: Lima-Verde
authors.affiliation: Department of Physiology, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil.
authors.forename: Lucindo J
authors.initials: LJ
authors.lastname: Quintans-Júnior
authors.affiliation: Gonçalo Moniz Research Center, Oswaldo Cruz Foundation, Salvador, Bahia, Brazil.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Bezerra
authors.affiliation: Department of Chemistry, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil.
authors.forename: Paulo C L
authors.initials: PC
authors.lastname: Nogueira
authors.affiliation: Department of Pharmacy, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil. Electronic address: left.ufs@hotmail.com.
authors.forename: Adriano A S
authors.initials: AA
authors.lastname: Araujo
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D029785:Cyperaceae / Q000737:chemistry*; D000431:Ethanol; D006801:Humans; D056724:Immunity, Humoral / Q000187:drug effects; D008297:Male; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology; D010936:Plant Extracts / Q000009:adverse effects* / Q000494:pharmacology*; D012997:Solvents; D021241:Spectrometry, Mass, Electrospray Ionization; D014867:Water
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D010636:Phenols; D010936:Plant Extracts; D012997:Solvents; D014867:Water; D000431:Ethanol
keywords: Antitumor; Apoptosis; Remirea maritima; Sarcoma 180; Toxicity; Tunel