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


RESULTS
FC 10 and 25mg/kg/day i.p. and 50mg/kg/day oral and Cas X 25mg/kg/day i.p. and 50mg/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 5mg/kg/day i.p. and 25 and 50mg/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.
['Ferreira|Paulo Michel Pinheiro|PMP|', 'Bezerra|Daniel Pereira|DP|', 'Silva|Jurandy do Nascimento|JDN|', 'da Costa|Marcília Pinheiro|MP|', 'Ferreira|José Roberto de Oliveira|JRO|', 'Alencar|Nylane Maria Nunes|NMN|', 'Figueiredo|Ingrid Samantha Tavares de|IST|', 'Cavalheiro|Alberto José|AJ|', 'Machado|Camila Maria Longo|CML|', 'Chammas|Roger|R|', 'Alves|Ana Paula Negreiros Nunes|APNN|', 'Moraes|Manoel Odorico de|MO|', 'Pessoa|Claudia|C|']
D000818:Animals D000972:Antineoplastic Agents, Phytogenic D037821:Casearia D045744:Cell Line, Tumor D049109:Cell Proliferation D045785:Diterpenes, Clerodane D005260:Female D006801:Humans D007668:Kidney D007958:Leukocyte Count D008099:Liver D008807:Mice, Inbred BALB C D008819:Mice, Nude D008853:Microscopy D009369:Neoplasms D010936:Plant Extracts D018515:Plant Leaves D047368:Tumor Burden
Casearin X Sarcoma 180 Hollow fiber assay Antineoplastic Leukogram Toxicity