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1.
Bioorg Chem ; 150: 107581, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38908129

RESUMO

In this study, we synthesized a new-generation library of colchicine derivatives via cycloaddition of colchicine utilizing position C-8 and C-12 diene system regioselectivity with aryne precursor to generate a small, focused library of derivatives. We assessed their anticancer activity against various cancer cell lines like MCF-7, MDA-MB-231, MDA-MB-453, and PC-3. Normal human embryonic kidney cell line HEK-293 was used to determine the toxicity. Among these derivatives, silicon-tethered compound B-4a demonstrated the highest potency against breast cancer cells. Subsequent mechanistic studies revealed that B-4a effectively modulates cell cycle regulatory kinases (CDK-2 and CDK-4) and their associated cyclins (cyclin-B1, cyclin-D1), inducing apoptosis. Additionally, B-4a displayed a noteworthy impact on tubulin polymerization, compared to positive control flavopiridol hydrochloride in a dose-dependent manner, and significantly disrupted the vimentin cytoskeleton, contributing to G1 arrest in breast cancer cells. Moreover, B-4a exhibited substantial anti-metastatic properties by inhibiting breast cancer cell migration and invasion. These effects are attributed to the down-regulation of major epithelial to mesenchymal transition (EMT) factors, including vimentin and Twist-1, and the upregulation of the epithelial marker E-cadherin in an apoptosis-dependent manner.


Assuntos
Antineoplásicos , Neoplasias da Mama , Proliferação de Células , Colchicina , Quinase 2 Dependente de Ciclina , Quinase 4 Dependente de Ciclina , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Transição Epitelial-Mesenquimal , Humanos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Quinase 2 Dependente de Ciclina/metabolismo , Quinase 2 Dependente de Ciclina/antagonistas & inibidores , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Relação Estrutura-Atividade , Estrutura Molecular , Proliferação de Células/efeitos dos fármacos , Colchicina/farmacologia , Colchicina/química , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 4 Dependente de Ciclina/metabolismo , Descoberta de Drogas , Feminino , Apoptose/efeitos dos fármacos , Reação de Cicloadição , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/síntese química , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos
2.
Turk Neurosurg ; 23(6): 700-6, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24310451

RESUMO

AIM: To study the clinicopathologic characteristics of chordomas from a single institution. MATERIAL AND METHODS: This study is a retrospective analysis of 18 cases of chordomas diagnosed over a period of 5-years at Sher-i-Kashmir Institute of Medical Sciences, Srinagar, from 2006 to 2010. RESULTS: The overall mean age of the patients was 46.72 years. Males outnumbered females. Sacrum was the commonest site involved. Histopathologically, the majority of cases were conventional chordoma with four cases of chondroid variety. There was a single case of dedifferentiated chordoma that presented with bone metastasis. Most patients did well after surgery and radiotherapy. One patient had a local recurrence and one patient with dedifferentiated variant died on follow-up. CONCLUSION: Though locally aggressive, chordomas are effectively treated with resection and postoperative radiotherapy.


Assuntos
Neoplasias Ósseas/cirurgia , Cordoma/cirurgia , Adolescente , Adulto , Idade de Início , Biópsia por Agulha Fina , Neoplasias Ósseas/epidemiologia , Neoplasias Ósseas/radioterapia , Cordoma/epidemiologia , Cordoma/radioterapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Índia/epidemiologia , Estimativa de Kaplan-Meier , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sacro/cirurgia , Fatores Sexuais , Análise de Sobrevida , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto Jovem
3.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-277282

RESUMO

Environmental pollution affects the quality of pedosphere, hydrosphere, atmosphere, lithosphere and biosphere. Great efforts have been made in the last two decades to reduce pollution sources and remedy the polluted soil and water resources. Phytoremediation, being more cost-effective and fewer side effects than physical and chemical approaches, has gained increasing popularity in both academic and practical circles. More than 400 plant species have been identified to have potential for soil and water remediation. Among them, Thlaspi, Brassica, Sedum alfredii H., and Arabidopsis species have been mostly studied. It is also expected that recent advances in biotechnology will play a promising role in the development of new hyperaccumulators by transferring metal hyperaccumulating genes from low biomass wild species to the higher biomass producing cultivated species in the times to come. This paper attempted to provide a brief review on recent progresses in research and practical applications of phytoremediation for soil and water resources.


Assuntos
Biodegradação Ambiental , Metais Pesados , Metabolismo , Poluentes do Solo , Metabolismo , Poluentes Químicos da Água , Metabolismo
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