Preclinical anticancer effectiveness of a fraction from Casearia sylvestris and its component Casearin X: in vivo and ex vivo methods and microscopy examinations
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Data
2016-06-20
Autores
Pinheiro Ferreira, Paulo Michel
Bezerra, Daniel Pereira
Silva, Jurandy do Nascimento
Costa, Marcilia Pinheiro da
Oliveira Ferreira, Jose Roberto de
Nunes Alencar, Nylane Maria
Tavares de Figueiredo, Ingrid Samantha
Cavalheiro, Alberto Jose [UNESP]
Longo Machado, Camila Maria [UNESP]
Chammas, Roger [UNESP]
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Elsevier B.V.
Resumo
Ethnopharmacological relevance: Casearia sylvestris (Salicaceae) is found in South America and presents antiulcerogenic, cytotoxic, antimicrobial, anti-inflammatory and antihypertensive activities. Aim of the study: To assess the in vivo and ex vivo antitumor action of a fraction with casearins (FC) and its main component- Casearin X-isolated from C sylvestris leaves. Materials and methods: Firstly, Sarcoma 180 bearing Swiss mice were treated with FC and Cas X for 7 days. Secondly, BALB/c nude animals received hollow fibers with colon carcinoma (HCT-116) or glioblastoma (SF-295) cells and were treated with FC for 4 days. On 5th day, proliferation was determined by MIT assay. Results: FC 10 and 25 mg/kg/day i.p. and 50 mg/kg/day oral and Cas X 25 mg/kg/day i.p. and 50 mg/kg/ day oral revealed tumor growth inhibition rates of 35.8, 86.2, 53.7, 90.0 and 65.5% and such tumors demonstrated rare mitoses and coagulation necrosis areas. Similarly, FC reduced multiplying of HCT-116 and SF-295 cells when evaluated by the Hollow Fiber Assay (2.5 and 5 mg/kg/day i.p. and 25 and 50 mg/ kg/day oral), with cell growth inhibition rates ranging from 33.3 to 67.4% (p < 0.05). Flow cytometry experiments revealed that FC reduced membrane integrity and induced DNA fragmentation and mitochondrial depolarization (p < 0.05). Conclusions: FC and Cas X were efficient antitumor substances against murine and human cancer cells and caused reversible morphological changes in liver, kidneys and spleens, emphasizing clerodane diterpenes as an emerging class of anticancer molecules. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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Casearin X, Hollow fiber assay, Sarcoma 180, Antineoplastic, Leukogram, Toxicity
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Journal Of Ethnopharmacology. Clare: Elsevier Ireland Ltd, v. 186, p. 270-279, 2016.