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1.
Environ Toxicol ; 36(9): 1848-1856, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34076342

RESUMO

Head and neck cancer is associated with poor prognosis because of its highly metastatic nature. For the better management of head and neck cancer patients, it is very important to diagnose the cancer at an early stage, as well as to prevent the rapid spread of cancer either through direct invasion or lymphatic metastasis. In present study, the effect of dehydrocrenatidine, which is a beta-carboline alkaloid found in the medicinal plant Picrasma quassioides, on human head and neck cancer metastasis was investigated. The study results revealed the treatment of FaDu, SCC9, and SCC47 cells with 5, 10, and 20 µM of dehydrocrenatidine significantly decreased the motility, migration, and invasion of head and neck cancer cells. Moreover, the dehydrocrenatidine treatment significantly decreased the expression of MMP-2 and phosphorylation of ERK1/2 and JNK1/2. Additional experiments revealed that the cotreatment of dehydrocrenatidine with either ERK1/2 or JNK1/2 inhibitor caused further reduction in cancer cell motility and migration compared to that in dehydrocrenatidine treatment alone. Moreover, similar trend was observed in case of ERK1/2 and JNK1/2 phosphorylation and MMP-2 expression after the cotreatment. Taken together, the mechanism by which dehydrocrenatidine can decrease the phosphorylation of ERK1/2 and JNK1/2, follow decrease the expression of MMP-2 and inhibits head and neck cancer cells invasion and migration. This present study identifies dehydrocrenatidine as a potent antimetastatic agent that can be used clinically to improve head and neck cancer prognosis.


Assuntos
Neoplasias de Cabeça e Pescoço , Metaloproteinase 2 da Matriz , Carbolinas , Linhagem Celular Tumoral , Movimento Celular , Humanos , Sistema de Sinalização das MAP Quinases , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Proteína Quinase 8 Ativada por Mitógeno/metabolismo , Proteína Quinase 9 Ativada por Mitógeno/metabolismo , Invasividade Neoplásica
2.
Oncol Rep ; 46(2)2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34165177

RESUMO

Nasopharyngeal carcinoma (NPC) is an indicator disease in Asia due to its unique geographical and ethnic distribution. Dehydrocrenatidine (DC) is a ß­carboline alkaloid abundantly present in Picrasma quassioides (D. Don) Benn, a deciduous shrub or small tree native to temperate regions of southern Asia, and ß­carboline alkaloids play anti­inflammatory and antiproliferative roles in various cancers. However, the mechanism and function of DC in human NPC cells remain only partially explored. The present study aimed to examine the cytotoxicity and biochemical role of DC in human NPC cells. The MTT method, cell cycle analysis, DAPI determination, Annexin V/PI double staining, and mitochondrial membrane potential examination were performed to evaluate the effects of DC treatment on human NPC cell lines. In addition, western blotting analysis was used to explore the effect of DC on apoptosis and signaling pathways in related proteins. The analysis results confirmed that DC significantly reduced the viability of NPC cell lines in a dose­ and time­dependent manner and induced apoptosis through internal and external apoptotic pathways (including cell cycle arrest, altered mitochondrial membrane potential, and activated death receptors). Western blot analysis illustrated that DC's effect on related proteins in the mitogen­activated protein kinase pathway can induce apoptosis by enhancing ERK phosphorylation and inhibiting Janus kinase (JNK) phosphorylation. Notably, DC induced apoptosis by affecting the phosphorylation of JNK and ERK, and DC and inhibitors (SP600125 and U0126) in combination restored the overexpression of p­JNK and p­ERK. To date, this is the first study to confirm the apoptosis pathway induced by DC phosphorylation of p­JNK and p­REK in human NPC. On the basis of evidence obtained from this study, DC targeting the inhibition of NPC cell lines may be a promising future strategy for NPC treatment.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Carbolinas/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Picrasma/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Fosforilação/efeitos dos fármacos , Extratos Vegetais/química
3.
Phytomedicine ; 58: 152805, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31022663

RESUMO

BACKGROUND: Developing resistance to chemotherapeutic drugs has become a major problem in the management of nasopharyngeal carcinoma (NPC). To overcome this issue, use of natural plant products as chemosensitizers is gaining importance at a fast pace. HYPOTHESIS/PURPOSE: The present study was designed to evaluate the cytotoxic effect and mode of action of a natural pentacyclic triterpenoid, celastrol, on cisplatin-resistant NPC cells. RESULTS: Study results revealed that celastrol treatment significantly reduced the viability of NPC cells in dose and time dependent manners, as compared to untreated control cells. The cytotoxic effect of celastrol was mediated by cell cycle arrest at G2/M phase and induction of intrinsic and extrinsic apoptotic pathways. With further analysis, we observed that celastrol-induced activation of caspases was accompanied by increased phosphorylation of MAPK pathway proteins, p38, ERK1/2. CONCLUSION: Taken together, our observation provides a novel insight on use of a natural plant product, celastrol, in the management of chemoresistant NPC.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Carcinoma Nasofaríngeo/tratamento farmacológico , Triterpenos/farmacologia , Caspases/efeitos dos fármacos , Caspases/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Cisplatino/farmacologia , Humanos , Triterpenos Pentacíclicos , Fosforilação , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
5.
Phytomedicine ; 23(13): 1545-1554, 2016 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-27823618

RESUMO

BACKGROUND: Polyphyllin G (also called polyphyllin VII), extract from rhizomes of Paris yunnanensis Franch, has been shown to have strong anticancer activities in a wide variety of human cancer cell lines. However, the underlying influences of autophagy in human oral squamous cell carcinoma (OSCC) remain unclear. METHODS: In this study, the roles of apoptosis and autophagy in polyphyllin G-induced death in human oral cancer cells were investigated. Moreover, the molecular mechanism of the anticancer effects of polyphyllin G in human oral cancer cells was investigated. RESULTS: The results revealed that polyphyllin G significantly inhibited cell proliferation in human oral cancer cells; it dose-dependently induced apoptosis in SAS and OECM-1 cells through caspase-3, -8, and -9 activation and poly (ADP-ribose) polymerase cleavage. In addition, changes were observed in Bcl-2 and proapoptosis-related protein expression in different human oral cancer cell lines. The expression of both LC3-II and beclin-1 was markedly increased, suggesting the induction of autophagy in polyphyllin G-treated oral cells. To further clarify whether polyphyllin G-induced apoptosis and autophagy depended on Akt/extracellular signal-regulated kinases (ERK)/c-Jun N-terminal kinases (JNK)/p38 mitogen-activated protein kinases (MAPK) signaling pathways, the cells were cotreated with inhibitors. The results demonstrated polyphyllin G-induced apoptosis in oral cells through the activation of ERK, Akt, p38 MAPK, and JNK, whereas ERK and JNK accounted for polyphyllin G-induced autophagy. CONCLUSION: This study is the first to demonstrate apoptosis and autophagy during polyphyllin G-induced cell death in human oral cancer cell lines. These results suggest that polyphyllin G is a promising candidate for developing antitumor drugs targeting human oral squamous cell carcinoma.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Melanthiaceae/química , Neoplasias Bucais/tratamento farmacológico , Saponinas/farmacologia , Caspases/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Neoplasias Bucais/patologia , Extratos Vegetais/farmacologia , Poli(ADP-Ribose) Polimerases/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
6.
Adv Ther ; 29(1): 71-7, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22161550

RESUMO

INTRODUCTION: This retrospective study evaluates the efficacy of palliative chemotherapy with a modified docetaxel, cisplatin, 5-fluorouracil (5-FU; "TPF" regimen) regimen (mTPF; reduced doses of docetaxel, cisplatin, and 5-FU with reduction of intravenous 5-FU from 4 days to 2 days) in Asian patients with recurrent and metastatic squamous cell carcinoma of head and neck (HNSCC) after surgery and adjuvant chemoradiation. METHODS: The mTPF regimen was used in this study. Fifty-five patients (from January 2007 to October 2009) received docetaxel on day 1, followed by cisplatin and 5-FU administered continuous infusion on day 2 for another 48 hours every 3 weeks for three to six cycles. RESULTS: The disease control rate was 81%. The overall response rate was 56%. Five patients achieved complete remission; 26 patients had partial remission; 14 patients had stable disease. Ten patients had disease progression. The metastatic sites that responded well to mTPF regimen (either complete or partial remission) were: neck lymph node, lung, liver, and skin. The median follow-up was 15 months (range 1-28 months). The median overall survival was 10 months (range 2-28 months). The common nonhematological toxicity was alopecia and the most common hematological adverse event was neutropenia. Thirty-one patients (56%) had grade 3-4 neutropenia. CONCLUSION: The mTPF chemotherapy regimen is efficacious for the palliative treatment of recurrent and metastatic HNSCC in Asian patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Células Escamosas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/administração & dosagem , Progressão da Doença , Docetaxel , Fluoruracila/administração & dosagem , Neoplasias de Cabeça e Pescoço/etnologia , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/tratamento farmacológico , Cuidados Paliativos , Indução de Remissão , Estudos Retrospectivos , Taxa de Sobrevida , Taxoides/administração & dosagem
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