RESUMO
BACKGROUND: Sulforaphane (SFN), a natural compound present in cruciferous vegetable, has been shown to possess anti-cancer activities. Cancer stem cell (CSC) in bulk tumor is generally considered as treatment resistant cell and involved in cancer recurrence. The effects of SFN on nasopharyngeal carcinoma (NPC) CSCs have not yet been explored. PURPOSE: The present study aims to examine the anti-tumor activities of SFN on NPC cells with CSC-like properties and the underlying mechanisms. METHODS: NPC cells growing in monolayer culture, CSCs-enriched NPC tumor spheres, and also the NPC nude mice xenograft were used to study the anti-tumor activities of SFN on NPC. The population of cells expressing CSC-associated markers was evaluated using flow cytometry and aldehyde dehydrogenase (ALDH) activity assay. The effect of DNA methyltransferase 1 (DNMT1) on the growth of NPC cells was analyzed by using small interfering RNA (siRNA)-mediated silencing method. RESULTS: SFN was found to inhibit the formation of CSC-enriched NPC tumor spheres and reduce the population of cells with CSC-associated properties (SRY (Sex determining Region Y)-box 2 (SOX2) and ALDH). In the functional study, SFN was found to restore the expression of Wnt inhibitory factor 1 (WIF1) and the effect was accompanied with the downregulation of DNMT1. The functional activities of WIF1 and DNMT1 were confirmed using exogenously added recombinant WIF1 and siRNA knockdown of DNMT1. Moreover, SFN was found to inhibit the in vivo growth of C666-1 cells and enhance the anti-tumor effects of cisplatin. CONCLUSION: Taken together, we demonstrated that SFN could suppress the growth of NPC cells via the DNMT1/WIF1 axis.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Antineoplásicos Fitogênicos/farmacologia , DNA (Citosina-5-)-Metiltransferase 1/metabolismo , Isotiocianatos/farmacologia , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Brassicaceae/química , Linhagem Celular Tumoral , Cisplatino/administração & dosagem , DNA (Citosina-5-)-Metiltransferase 1/genética , Humanos , Isotiocianatos/administração & dosagem , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/patologia , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição SOXB1/metabolismo , Sulfóxidos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Exfoliated graphene oxide (EG)/MoO2 composites are synthesized by a simple solid-state graphenothermal reduction method. Graphene oxide (GO) is used as a reducing agent to reduce MoO3 and as a source for EG. The formation of different submicron sized morphologies such as spheres, rods, flowers, etc., of monoclinic MoO2 on EG surfaces is confirmed by complementary characterization techniques. As-synthesized EG/MoO2 composite with a higher weight percentage of EG performed excellently as an anode material in lithium-ion batteries. The galvanostatic cycling studies aided with postcycling cyclic voltammetry and galvanostatic intermittent titrations followed by ex situ structural studies clearly indicate that Li intercalation into MoO2 is transformed into conversion upon aging at low current densities while intercalation mechanism is preferably taking place at higher current rates. The intercalation mechanism is found to be promising for steady-state capacity throughout the cycling because of excess graphene and higher current density even in the operating voltage window of 0.005-3.0 V in which MoO2 undergoes conversion below 0.8 V.
RESUMO
This study was conducted to determine whether a particular Chinese medicinal preparation is effective in alleviating menopausal symptoms. Chinese women with menopausal symptoms were recruited to receive treatment for 3 months followed by 3 months without treatment. The severity of menopausal symptoms and serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol levels were assessed at baseline, 3 and 6 months. Data from 97 women with a mean age of 52.3 years were analyzed. Sixty women (62%) were postmenopausal. The serum FSH level (interquartile range) was 58.0 (39.5-72.4) IU/l at baseline and rose significantly 3 months after treatment. The difference remained significant in the postmenopausal group while there was no significant difference in the perimenopausal women. The changes in serum LH and estradiol levels remained unchanged. The baseline menopausal symptom score was 8.9 +/- 6.0. The menopausal symptom score improved markedly after treatment and remained at the same level at 6 months. All individual menopausal symptoms improved significantly after 3 months of treatment except dry eye. Most of these symptoms remained significantly improved at 6 months compared with the pre-treatment assessment. We observed that the Chinese medicinal preparation used in this study is effective in improving menopausal symptoms in healthy Chinese women. Further randomized controlled trial will be needed to confirm this observation.