RESUMEN
BACKGROUND: Osteosarcoma is the most common primary bone malignancy of adolescents and young adults. METHODS: We analyzed liver X receptor α (LXRα) mRNA expression in 16 pairs of human osteosarcoma tissues and adjacent noncancerous tissues. Moreover, we investigated LXRα's potential role in regulating cell proliferation in Saos-2 and U2OS cells. RESULTS: We found that activation of LXRα, a member of nuclear receptor, was able to inhibit cell proliferation in Saos-2 and U2OS cells. At the molecular level, our results further revealed that expression of tumor suppressor gene, FoxO1, was up-regulated by LXRα activation. LXRα activates FoxO1 transcription through a direct binding on its promoter region. CONCLUSION: LXRα acts as a tumor suppressor for osteosarcoma, which may offer a new way in molecular targeting cancer treatment.
Asunto(s)
Factores de Transcripción Forkhead/metabolismo , Receptores Nucleares Huérfanos/metabolismo , Sitios de Unión , Línea Celular Tumoral , Proliferación Celular , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Proteína Forkhead Box O1 , Factores de Transcripción Forkhead/genética , Humanos , Receptores X del Hígado , Receptores Nucleares Huérfanos/genética , Osteosarcoma/metabolismo , Osteosarcoma/patología , Regiones Promotoras Genéticas , Interferencia de ARN , ARN Mensajero/metabolismo , ARN Interferente Pequeño/metabolismo , Transcripción Genética , Regulación hacia ArribaRESUMEN
BACKGROUND: Osteoporosis is a common disease in aging populations. However, osteoporosis treatment is still challenging. Here, we aimed to investigate the role of neohesperidin (NEO) in osteoporosis progression and the potential mechanism. METHODS: Bone mesenchymal stem cells (BMSCs) were isolated and treated with different concentrations of NEO (0, 10, 30, 100 µM). Cell proliferation was analyzed by cell count kit-8 (CCK-8) assay. RNA-sequencing was performed on the isolated BMSCs with control and NEO treatment. Differentially expressed genes were obtained by R software. Alkaline phosphatase (ALP) staining and Alizarin red staining (ARS) were performed to assess the osteogenic capacity of the NEO. qRT-PCR was used to detect the expression of osteoblast markers. Western blot was used to evaluate the protein levels in BMSCs. RESULTS: NEO treatment significantly improved hBMSC proliferation at different time points, particularly when cells were incubated with 30 µM NEO (P < 0.05). NEO dose-dependently increased the ALP activity and calcium deposition than the control group (P < 0.05). A total of 855 differentially expressed genes were identified according to the significance criteria of log2 (fold change) > 1 and adj P < 0.05. DKK1 partially reversed the promotion effects of NEO on osteogenic differentiation of BMSCs. NEO increased levels of the ß-catenin protein in BMSCs. CONCLUSION: NEO plays a positive role in promoting osteogenic differentiation of BMSCs, which was related with activation of Wnt/ß-catenin pathway.
Asunto(s)
Huesos/citología , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/genética , Hesperidina/análogos & derivados , Células Madre Mesenquimatosas/fisiología , Osteogénesis/efectos de los fármacos , Osteogénesis/genética , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Vía de Señalización Wnt/efectos de los fármacos , Vía de Señalización Wnt/genética , beta Catenina/metabolismo , Fosfatasa Alcalina/metabolismo , Calcio/metabolismo , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Células Cultivadas , Relación Dosis-Respuesta a Droga , Hesperidina/farmacología , Humanos , Células Madre Mesenquimatosas/metabolismo , Osteoporosis/genética , Osteoporosis/metabolismo , Osteoporosis/patologíaRESUMEN
Recently, the Populus yunnanensis extract has drawn the attention of most researchers, because of their anti-cancer activity. In this present research, the anti-cancer activity of the Populus yunnanensis extract was measured with Cell Counting Kit-8 (CCK-8) detection kit on the cancer cells. Then, the inhibitory activity of the Populus yunnanensis extract on the migration and invasion ability of the cancer cells was also determined in this present research with trans-well assay. Subsequently, to reveal the evolutionary genome evolution evaluation of the Populus yunnanensis and other Populus species, the high-throughput Illumina pair-end sequencing was performed and the chloroplast (cp) genome of Populus yunnanensis was determined, and the phylogenetic analysis was finished as wells. The results of the CCK-8 assay indicated that the Populus yunnanensis extract showed inhibitory effect on the cancer cell viability. Besides, the migration and invasion ability of the cancer cell was also reduced by the Populus yunnanensis extract. The complete chloroplast genome sequence results revealed that the Populus yunnanensis has a 156,505 bp circular cp genome. The phylogenetic analysis further revealed that the Populus yunnanensis has closely relationship with Populus simonii.
Asunto(s)
Antineoplásicos Fitogénicos , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Cloroplastos/genética , Genoma de Planta/genética , Osteosarcoma/patología , Extractos Vegetales/farmacología , Populus/química , Populus/genética , Secuenciación Completa del Genoma/métodos , Humanos , Invasividad Neoplásica , Filogenia , Células Tumorales CultivadasRESUMEN
Rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs) proliferate abnormally and resist apoptosis. Bufalin inhibits cell proliferation and induces apoptosis in human cancer cells. In this study, we explored the effects of bufalin on interleukin-1beta (IL-1ß)-induced proliferation and apoptosis of RAFLSs. The cell proliferation and apoptosis were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay and annexin V/propidium iodide staining, respectively. Bufalin dose-dependently inhibited IL-1ß-induced RAFLS proliferation. Mechanistically, bufalin decreased the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB), both of which are involved in IL-1ß-mediated RAFLS proliferation. Moreover, bufalin induced apoptosis and mitochondrial damage of RAFLSs, which was associated with Bcl-2 downregulation, Bax upregulation, mitochondrial cytochrome c release, and enhanced cleavages of caspase-3 and poly-(ADP-ribose) polymerase. Collectively, our results reveal that bufalin suppresses IL-1ß-induced proliferation of RAFLSs through MAPK and NF-κB signaling pathways and induces RAFLS apoptosis via the mitochondria-dependent pathway.