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1.
Sci Rep ; 11(1): 21527, 2021 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-34728751

RESUMO

This study aimed to investigate the anticancer activity of dried-pericarp water extract of fermented C. japonicus (CJ). The dried-pericarp water extracts of CJ were fermented using Aspergillus oryzae and Saccharomyces cerevisiae at 30 °C and 35 °C. The anticancer activities of both water extracts fermented at 30 °C and 35 °C using A. oryzae against FaDu cells were remarkably changed compared with unfermented dried-pericarp water extract of CJ, which has no anticancer activity. Cleaved-PARP, caspase 3, and apoptotic cells stained with annexin V/PI were significantly increased by treatment with A. oryzae extracts fermented at 30 °C. The insulin-like growth factor-binding protein 2 (IGFBP-2) protein level and mTOR phosphorylation by A. oryzae fermented extracts (AOFE) were dramatically reduced, and the expression levels of IGFBP-2 and phosphorylated mTOR were significantly increased depending on the glucose concentrations in FaDu cells. These results suggested that the cell viabilities in AOFE were restored as the glucose concentrations increased. Furthermore, it was confirmed LC/MS/MS that the content of gallic acid was increased by fermentation of Aspergillus oryzae (5.596 ± 0.1746 µg/mg) compared to the unfermented extract (1.620 ± 0.0432 µg/mg). Based on these results, the anticancer effect of AOFE was achieved through inhibition of the IGFBP-2/mTOR signaling pathway. These results suggest that AOFE may be a potential treatment for head and neck cancer.


Assuntos
Antineoplásicos/farmacologia , Aspergillus oryzae/química , Camellia/química , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Extratos Vegetais/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Fermentação , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Serina-Treonina Quinases TOR/genética , Células Tumorais Cultivadas , Água/química
2.
Anticancer Agents Med Chem ; 17(11): 1519-1525, 2017 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-28356020

RESUMO

BACKGROUND: Fruits of Morus alba L. (mulberry) have various bioactive compounds such as polyphenols and anthocyanins and used as a herbal medicine. However, the anti-cancer effects and molecular basis have not been elucidated. METHODS: We isolated the cyanidin-3-glucoside in various cultivar of mulberry by acidified-methanol extraction methods. This molecule were compared mass spectroscopic properties by LC-MS/MS and analyzed by 1H and 13C NMR. We examined the anti-cancer effect with molecular mechanisms of the cyanidin-3-glucoside on MDA-MB-453 human breast cancer cells and xenograft animal model. RESULTS: The treatment with the mulberry cyanidin-3-glucoside decreased cell viability in a dose-dependent manner with alteration of apoptotic protein contents, and DNA fragmentation, suggesting that cells undergo apoptosis. Supporting the observations, Treatment with the cyanidin-3-glucoside showed active apoptosis by caspase-3 cleavage and DNA fragmentation through Bcl-2 and Bax pathway. Indeed, cyanidin-3-glucoside inhibits tumor growth in MDA-MB-453 cells-inoculated nude mice. Tumor growth of xenograft nude mouse was significantly reduced compared to the control group by the cyanidin-3-glucoside. CONCLUSION: The data demonstrate that cyanidin-3-glucoside isolated from mulberry induced apoptosis in breast cancer (MDA-MB-453) cells, and therefore, has a potential as an anti-cancer agent. These results show that mulberry cyanidin-3-glucoside inhibit the proliferation and growth in vitro and in vivo model and, indicating the inhibition of tumor progression.


Assuntos
Antocianinas/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Caspase 3/metabolismo , Fragmentação do DNA/efeitos dos fármacos , Glucosídeos/farmacologia , Morus/química , Animais , Antocianinas/química , Antocianinas/metabolismo , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Glucosídeos/química , Glucosídeos/metabolismo , Humanos , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Endogâmicos ICR , Estrutura Molecular , Relação Estrutura-Atividade , Células Tumorais Cultivadas
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