title: In vitro and in vivo antitumor effect of trachylobane-360, a diterpene from Xylopia langsdorffiana.
abstract: Trachylobane-360 (ent-7α-acetoxytrachyloban-18-oic acid) was isolated from Xylopia langsdorffiana. Studies have shown that it has weak cytotoxic activity against tumor and non-tumor cells. This study investigated the in vitro and in vivo antitumor effects of trachylobane-360, as well as its cytotoxicity in mouse erythrocytes. In order to evaluate the in vivo toxicological aspects related to trachylobane-360 administration, hematological, biochemical and histopathological analyses of the treated animals were performed. The compound exhibited a concentration-dependent effect in inducing hemolysis with HC₅₀ of 273.6 µM, and a moderate in vitro concentration-dependent inhibitory effect on the proliferation of sarcoma 180 cells with IC₅₀ values of 150.8 µM and 150.4 µM, evaluated by the trypan blue exclusion test and MTT reduction assay, respectively. The in vivo inhibition rates of sarcoma 180 tumor development were 45.60, 71.99 and 80.06% at doses of 12.5 and 25 mg/kg of trachylobane-360 and 25 mg/kg of 5-FU, respectively. Biochemical parameters were not altered. Leukopenia was observed after 5-FU treatment, but this effect was not seen with trachylobane-360 treatment. The histopathological analysis of liver and kidney showed that both organs were mildly affected by trachylobane-360 treatment. Trachylobane-360 showed no immunosuppressive effect. In conclusion, these data reinforce the anticancer potential of this natural diterpene.
authors.affiliation: Laboratory of Pharmaceutical Technology, Federal University of Paraíba, P.O. Box 5009, João Pessoa 58051-970, PB, Brazil. joaocpita@yahoo.com.br
authors.forename: João Carlos Lima Rodrigues
authors.initials: JC
authors.lastname: Pita
authors.forename: Aline Lira
authors.initials: AL
authors.lastname: Xavier
authors.forename: Tatyanna Kelvia Gomes
authors.initials: TK
authors.lastname: de Sousa
authors.forename: Vivianne Mendes
authors.initials: VM
authors.lastname: Mangueira
authors.forename: Josean Fechine
authors.initials: JF
authors.lastname: Tavares
authors.forename: Robson José
authors.initials: RJ
authors.lastname: de Oliveira Júnior
authors.forename: Robson Cavalcante
authors.initials: RC
authors.lastname: Veras
authors.forename: Hilzeth de Luna Freire
authors.initials: Hde L
authors.lastname: Pessoa
authors.forename: Marcelo Sobral
authors.initials: MS
authors.lastname: da Silva
authors.forename: Sandra
authors.initials: S
authors.lastname: Morelli
authors.forename: Veridiana de Melo Rodrigues
authors.initials: Vde M
authors.lastname: Ávila
authors.forename: Teresinha Gonçalves
authors.initials: TG
authors.lastname: da Silva
authors.forename: Margareth de Fátima Formiga Melo
authors.initials: Mde F
authors.lastname: Diniz
authors.forename: Marianna Vieira Sobral
authors.initials: MV
authors.lastname: Castello-Branco
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004224:Diterpenes / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006403:Hematologic Tests; D006461:Hemolysis / Q000187:drug effects; D020128:Inhibitory Concentration 50; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D012510:Sarcoma 180 / Q000188:drug therapy* / Q000473:pathology; D014184:Transplantation, Homologous; D047368:Tumor Burden / Q000187:drug effects; D054336:Xylopia / Q000737:chemistry*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004224:Diterpenes; C572780:ent-7alpha-acetoxytrachyloban-18-oic acid