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1.
Molecules ; 23(6)2018 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-29914196

RESUMO

Ovarian cancer has the highest mortality rate of all gynecological malignancies and the five-year death rate of patients has remained high in the past five decades. Recently, with the rise of cancer stem cells (CSCs) theory, an increasing amount of research has suggested that CSCs give rise to tumor recurrence and metastasis. Theasaponin E1 (TSE1), which was isolated from green tea (Camellia sinensis) seeds, has been proposed to be an effective compound for tumor treatment. However, studies on whether TSE1 takes effect through CSCs have rarely been reported. In this paper, ALDH-positive (ALDH+) ovarian cancer stem-like cells from two platinum-resistant ovarian cancer cell lines A2780/CP70 and OVCAR-3 were used to study the anti-proliferation effect of TSE1 on CSCs. The ALDH+ cells showed significantly stronger sphere forming vitality and stronger cell migration capability. In addition, the stemness marker proteins CD44, Oct-4, Nanog, as well as Bcl-2 and MMP-9 expression levels of ALDH+ cells were upregulated compared with the original tumor cells, indicating that they have certain stem cell characteristics. At the same time, the results showed that TSE1 could inhibit cell proliferation and suspension sphere formation in ALDH+ cells. Our data suggests that TSE1 as a natural compound has the potential to reduce human ovarian cancer mortality. However, more research is still needed to find out the molecular mechanism of TSE1-mediated inhibition of ALDH+ cells and possible drug applications on the disease.


Assuntos
Aldeído Desidrogenase/metabolismo , Células-Tronco Neoplásicas/metabolismo , Ácido Oleanólico/análogos & derivados , Neoplasias Ovarianas/metabolismo , Saponinas/farmacologia , Biomarcadores/metabolismo , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Estrutura Molecular , Células-Tronco Neoplásicas/efeitos dos fármacos , Ácido Oleanólico/química , Ácido Oleanólico/farmacologia , Neoplasias Ovarianas/tratamento farmacológico , Saponinas/química , Chá/química
2.
Molecules ; 22(10)2017 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-28974006

RESUMO

Ovarian cancer is regarded as one of the most severe malignancies for women in the world. Death rates have remained steady over the past five decades, due to the undeniable inefficiency of the current treatment in preventing its recurrence and death. The development of new effective alternative agents for ovarian cancer treatment is becoming increasingly critical. Tea saponins (TS) are triterpenoidsaponins composed of sapogenins, glycosides, and organic acids, which possess a variety of pharmacological activities, and have shown promise in the anti-cancer field. Through cell CellTiter 96® Aqueous One Solution Cell Proliferation assay (MTS) assay, colony formation, Hoechst 33342 staining assay, caspase-3/7 activities, flow cytometry for apoptosis analysis, and Western blot, we observed that TS isolated from the seeds of tea plants, Camellia sinensis, exhibited strong anti-proliferation inhibitory effects on OVCAR-3 and A2780/CP70 ovarian cancer cell lines. Our results indicate that TS may selectivity inhibit human ovarian cancer cells by mediating apoptosis through the extrinsic pathway, and initiating anti-angiogenesis via decreased VEGF protein levels in a HIF-1α-dependent pathway. Our data suggests that, in the future, TS could be incorporated into a potential therapeutic agent against human ovarian cancer.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Neoplasias Ovarianas/tratamento farmacológico , Saponinas/química , Saponinas/farmacologia , Triterpenos/química , Triterpenos/farmacologia , Apoptose , Camellia sinensis/química , Técnicas de Cultura de Células , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Ácido Oleanólico/química , Extratos Vegetais/química , Saponinas/isolamento & purificação , Sementes/química , Transdução de Sinais , Chá/química , Triterpenos/isolamento & purificação , Fator A de Crescimento do Endotélio Vascular/efeitos dos fármacos
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