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1.
J Ethnopharmacol ; 276: 114131, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-33894284

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Breast cancer is a serious threat in low-income as well as developed countries. To face this, many herbal preparations are prescribed by traditional healers in Cameroon, among which is Anonidium mannii commonly called "wild soursop". AIM: This study was undertaken to assess the anti-tumor effect of A. mannii ethanolic extract on cancer cell growth and against DMBA-induced mammary tumors in rats. MATERIALS AND METHODS: The well characterized MTT bioassay was used to assess the cytotoxic potential of A. mannii ethanolic extract in liver (HepG2), prostate (DU145 & PC3) and breast (MCF-7) cancer cell lines. Considering the fact that breast cells were the most sensitive to the extract, a 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast tumor rat model was used to assess the possible anticancer effect of A. mannii extract. Indeed, rats were treated with either tamoxifen (3.3 mg/kg BW) or A. mannii extract (16.5, 50 and 150 mg/kg BW) or vehicle (2% ethanol) for 20 weeks. Tumor incidence, tumor mass and volume, oxidative stress status in tumor as well as tumor histoarchitecture were evaluated. RESULTS: A 24 h incubation of tested cells with the A. mannii extract significantly slowed cell growth in a concentration-dependent manner with an interesting effect in breast cells (IC50 ~61.5 µg/mL). As compared to the DMBA rats, those treated with A. mannii extract (50 and 150 mg/kg) showed reduced breast tumor incidence (28%), tumor burden (95.34% at 50 mg/kg and 99.14% at 150 mg/kg) and tumor volume (~92%). A. mannii extract counteracted the high proliferation of terminal mammary ducts induced by DMBA, mainly at 50 mg/kg. Furthermore, the extract decreased MDA and nitrite levels but increased SOD activity in the mammary gland. High Performance Liquid Chromatography coupled with Mass Spectrometry (HPLC-MS) analysis detected potential anticancer and antioxidant alkaloids in A. manni extract, which are close to those found in Annona muricata. CONCLUSION: These results provide evidence on the in vitro and in vivo anticancer effects of A. mannii, and therefore support its use in traditional medicine system to fight against cancer.


Assuntos
Alcaloides/farmacologia , Annonaceae/química , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Neoplasias Mamárias Experimentais/prevenção & controle , Extratos Vegetais/farmacologia , Alcaloides/uso terapêutico , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/uso terapêutico , Antineoplásicos Fitogênicos/toxicidade , Antioxidantes/química , Antioxidantes/uso terapêutico , Antioxidantes/toxicidade , Camarões , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Etanol/química , Feminino , Humanos , Neoplasias Mamárias Experimentais/sangue , Neoplasias Mamárias Experimentais/patologia , Medicina Tradicional , Minerais/análise , Tamanho do Órgão/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Casca de Planta/química , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Extratos Vegetais/toxicidade , Ratos Wistar , Espectrometria de Massas por Ionização por Electrospray , Tamoxifeno/uso terapêutico , Carga Tumoral/efeitos dos fármacos
2.
J Ethnopharmacol ; 190: 183-99, 2016 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-27267829

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Crateva adansonii DC is a plant traditionally used in Cameroon to treat constipation, asthma, snakebites, postmenopausal complaints and cancers. AIM: The anticancer potential of the dichloromethane/methanol extract of C. adansonii stem barks was investigated using human breast cancer cell and 7,12 dimethylbenz(a)anththracene (DMBA)-induced mammary tumorigenesis model in rats. MATERIAL AND METHODS: The cytotoxicity of C. adansonii extract was assessed in vitro towards breast carcinoma (MCF-7 and MDA-MB-231) and non-tumoral cell lines (NIH/3T3 and HUVEC) by Alamar Blue assay. Furthermore, in vivo studies were performed on female Wistar rats treated either with C. adansonii extract at a dose of 75 or 300mg/kg body weight or with tamoxifen (3.3mg/kg body weight), starting 1 week prior DMBA treatment and lasted 12 weeks. The investigation focused on tumour burden, tumour DNA fingerprint, morphological, histological, hematological, and biochemical parameters. RESULTS: CC50 values for the in vitro assays were 289µg/mL against MCF-7 cells and >500µg/mL in others cells, leading to a selectivity index ≥1.73. C. adansonii extract significantly (p<0.001) revealed in vivo the reduction of the cumulative tumour yield (87.23%), total tumour burden (88.64%), average tumour weight (71.11%) and tumour volume (78.07%) at the dose of 75mg/kg as compared to DMBA control group. A weak effect was also observed at 300mg/kg. This extract showed a moderate hyperplasia at the dose of 75mg/kg while at 300mg/kg no significant change was noted as compared to DMBA group. It protected rats from the DNA alteration induced by DMBA and increased antioxydant enzymes activities in mammary gland tissue homogenates. In addition, Ultra-High Performance Liquid Chromatography/ESI-QTOF-Mass Spectrometry analysis of C. adansonii extract detected structure-related of many well-known anticancer agents such as flavane gallate, flavonol, phenylpropanoïds, sesquiterpene derivatives, gallotannins and lignans. The LD50 of C. adansonii was estimated to be greater than 5000mg/kg. CONCLUSIONS: These aforementioned results suggest that the C. adansonii extract may possess antitumor constituents, which could combat breast cancer and prevent chemically-induced breast cancer in rats.


Assuntos
Anticarcinógenos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Capparaceae/química , Neoplasias Mamárias Experimentais/prevenção & controle , Extratos Vegetais/farmacologia , 9,10-Dimetil-1,2-benzantraceno , África , Animais , Anticarcinógenos/química , Anticarcinógenos/isolamento & purificação , Anticarcinógenos/toxicidade , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/toxicidade , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Cromatografia Líquida , Dano ao DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Etnobotânica , Feminino , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Concentração Inibidora 50 , Dose Letal Mediana , Células MCF-7 , Neoplasias Mamárias Experimentais/induzido quimicamente , Neoplasias Mamárias Experimentais/patologia , Medicinas Tradicionais Africanas , Camundongos , Estrutura Molecular , Células NIH 3T3 , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Plantas Medicinais , Ratos Wistar , Espectrometria de Massas por Ionização por Electrospray , Tamoxifeno/farmacologia , Fatores de Tempo , Carga Tumoral/efeitos dos fármacos
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