title: Antitumor and anti-cachectic effects of shark liver oil and fish oil: comparison between independent or associative chronic supplementation in Walker 256 tumor-bearing rats.
abstract: BACKGROUND
  Shark liver oil (SLOil) and fish oil (FOil), which are respectively rich in alkylglycerols (AKGs) and n-3 polyunsaturated fatty acids (PUFAs), are able to reduce the growth of some tumors and the burden of cachexia. It is known that FOil is able to reduce proliferation rate and increase apoptotic cells and lipid peroxidation of tumor cells efficiently. However, there are few reports revealing the influence of SLOil on these parameters. In the current study, effects of FOil chronic supplementation on tumor growth and cachexia were taken as reference to compare the results obtained with SLOil supplementation. Also, we evaluated if the association of SLOil and FOil was able to promote additive effects.
  
  
  METHODS
  Weanling male Wistar rats were divided into 4 groups: fed regular chow (C), supplemented (1 g/kg body weight) with SLOil (CSLO), FOil (CFO) and both (CSLO + FO). After 8 weeks half of each group was inoculated with Walker 256 cells originating new groups (W, WSLO, WFO and WSLO + FO). Biochemical parameters of cachexia, tumor weight, hydroperoxide content, proliferation rate and percentage of apoptotic tumor cells were analysed. Fatty acids and AKG composition of tumor and oils were obtained by high performance liquid chromatography and gas chromatography - mass spectrometry, respectively. Statistical analysis was performed by unpaired t-test and one-way ANOVA followed by a post hoc Tukey test.
  
  
  RESULTS
  Fourteen days after inoculation, SLOil was able to restore cachexia parameters to control levels, similarly to FOil. WSLO rats presented significantly lower tumor weight (40%), greater tumor cell apoptosis (~3-fold), decreased tumor cell proliferation (35%), and higher tumor content of lipid hydroperoxides (40%) than observed in W rats, but FOil showed more potent effects. Supplementation with SLOil + FOil did not promote additive effects. Additionally, chromatographic results suggested a potential incorporation competition between the n-3 fatty acids and the AKGs in the tumor cells' membranes.
  
  
  CONCLUSIONS
  SLOil is another marine source of lipids with similar FOil anti-cachectic capacity. Furthermore, despite being less potent than FOil, SLOil presented significant in vivo antitumor effects. These results suggest that the chronic supplementation with SLOil may be adjuvant of the anti-cancer therapy.
authors.affiliation: Area of Biological and Health Sciences, West University of Santa Catarina, Joaçaba, Brazil. fabiola.iagher@unoesc.edu.br.
authors.forename: Fabíola
authors.initials: F
authors.lastname: Iagher
authors.forename: Sérgio Ricardo
authors.initials: SR
authors.lastname: de Brito Belo
authors.forename: Wanessa Mazanek
authors.initials: WM
authors.lastname: Souza
authors.forename: Juliana Rehlander
authors.initials: JR
authors.lastname: Nunes
authors.forename: Katya
authors.initials: K
authors.lastname: Naliwaiko
authors.forename: Guilherme Lanzi
authors.initials: GL
authors.lastname: Sassaki
authors.forename: Sandro José Ribeiro
authors.initials: SJ
authors.lastname: Bonatto
authors.forename: Heloísa Helena Paro
authors.initials: HH
authors.lastname: de Oliveira
authors.forename: Gleisson Alisson Pereira
authors.initials: GA
authors.lastname: Brito
authors.forename: Carina
authors.initials: C
authors.lastname: de Lima
authors.forename: Marcelo
authors.initials: M
authors.lastname: Kryczyk
authors.forename: Carine Ferreira
authors.initials: CF
authors.lastname: de Souza
authors.forename: Jovani Antonio
authors.initials: JA
authors.lastname: Steffani
authors.forename: Everson Araújo
authors.initials: EA
authors.lastname: Nunes
authors.forename: Luiz Cláudio
authors.initials: LC
authors.lastname: Fernandes
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002100:Cachexia / Q000150:complications / Q000178:diet therapy* / Q000378:metabolism / Q000473:pathology; D002279:Carcinoma 256, Walker / Q000150:complications / Q000178:diet therapy* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D019587:Dietary Supplements; D005227:Fatty Acids / Q000378:metabolism; D005395:Fish Oils / Q000302:isolation & purification / Q000494:pharmacology*; D008401:Gas Chromatography-Mass Spectrometry; D006861:Hydrogen Peroxide / Q000819:agonists / Q000378:metabolism; D008099:Liver / Q000737:chemistry*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012754:Sharks / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects; D014886:Weaning
chemical_list: D000970:Antineoplastic Agents; D005227:Fatty Acids; D005395:Fish Oils; D006861:Hydrogen Peroxide