Preclinical anticancer effectiveness of a fraction from Casearia sylvestris and its component Casearin X: in vivo and ex vivo methods and microscopy examinations

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]; Negreiros Nunes Alves, Ana Paula; Moraes, Manoel Odorico de; Pessoa, Claudia

Preclinical anticancer effectiveness of a fraction from Casearia sylvestris and its component Casearin X: in vivo and ex vivo methods and microscopy examinations

Arquivos

WOS000377832000029.pdf (2.13 MB)

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

Longo Machado, Camila Maria

Chammas, Roger

Editor

Elsevier B.V.

Tipo

Artigo

Direito de acesso

Acesso aberto

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.