Zika virus (ZIKV) has been associated with serious health conditions, and an intense search to discover different ways to prevent and treat ZIKV infection is underway. Berberine and emodin possess several pharmacological properties and have been shown to be particularly effective against the entry and replication of several viruses. We show that emodin and berberine trigger a virucidal effect on ZIKV. When the virus was exposed to 160 µM of berberine, a reduction of 77.6% in the infectivity was observed; when emodin was used (40 µM), this reduction was approximately 83.3%. Dynamic light scattering data showed that both compounds significantly reduce the hydrodynamic radius of virus particle in solution. We report here that berberine and emodin, two natural compounds, have strong virucidal effect in Zika virus.
BackgroundGlypican 3 (GPC3) is a member of the family of glypican heparan sulfate proteoglycans (HSPGs). The GPC3 gene may play a role in controlling cell migration, negatively regulating cell growth and inducing apoptosis. GPC3 is downregulated in several cancers, which can result in uncontrolled cell growth and can also contribute to the malignant phenotype of some tumors. The purpose of this study was to analyze the mechanism of action of the GPC3 gene in clear cell renal cell carcinoma.MethodsFive clear cell renal cell carcinoma cell lines and carcinoma samples were used to analyze GPC3 mRNA expression (qRT-PCR). Then, representative cell lines, one primary renal carcinoma (786-O) and one metastatic renal carcinoma (ACHN), were chosen to carry out functional studies. We constructed a GPC3 expression vector and transfected the renal carcinoma cell lines, 786-O and ACHN. GPC3 overexpression was analyzed using qRT-PCR and immunocytochemistry. We evaluated cell proliferation using MTT and colony formation assays. Flow cytometry was used to evaluate apoptosis and perform cell cycle analyses.ResultsWe observed that GPC3 is downregulated in clear cell renal cell carcinoma samples and cell lines compared with normal renal samples. GPC3 mRNA expression and protein levels in 786-O and ACHN cell lines increased after transfection with the GPC3 expression construct, and the cell proliferation rate decreased in both cell lines following overexpression of GPC3. Further, apoptosis was not induced in the renal cell carcinoma cell lines overexpressing GPC3, and there was an increase in the cell population during the G1 phase in the cell cycle.ConclusionWe suggest that the GPC3 gene reduces the rate of cell proliferation through cell cycle arrest during the G1 phase in renal cell carcinoma.
Nanomedical approaches are the major transforming factor in cancer therapies. Based on important previous works in the field of drug delivery nanomaterials, recent years have brought a broad array of new and improved intelligent nanoscale platforms that are suited to deliver drugs. In this context, the purpose of this study was to investigate the action of different nanoemulsions designed to encapsulate chloroaluminum phthalocyanine, a hydrophobic photosensitizer used in photodynamic therapy, and doxorubicin, a well-known chemotherapeutic agent used to treat aggressive breast cancer cells. The mean nanostructured system size ranged from 170.8 to 181.0 nm, and the nanoemulsions presented spherical morphology. All formulations exhibited negative zeta potential values (-68.7 to -75.0 mV) and suitable polydispersity values (0.20 to 0.28), explaining their colloidal stability up to three months. Murine breast cancer cells (4T1) were incubated with nanoemulsions for three hours at various concentrations and were subjected to cell viability tests to find the concentration dependence profile. Thereafter, the in vitro phototoxic effect was evaluated in the presence of the visible laser light irradiation. Less than 10% of 4T1 viable cells were observed when photodynamic therapy and chemotherapy were combined at a 1.0 J · cm-2 laser light dose with 1.0 μM phthalocyanine and 0.5 μM doxorubicin. The cell death assay and cell cycle arrest analysis confirmed the therapy efficiency demonstrating an increase in the apoptosis rate and in the cell cycle arrest on G2. Additionally, 15 genes related to apoptosis and 25 target genes of anti-cancer drugs were overexpressed. Four genes related to apoptosis and four target genes of anti-cancer drugs were downregulated in 4T1 cells after treatment with nanoemulsion with phthalocyanine and doxorubicin associated with photodynamic therapy. Thus, the nanoemulsions loaded with phthalocyanine and doxorubicin presented appropriate physical stability, improved photophysical properties, and remarkable activity in vitro to be considered as promising formulations for photodynamic therapy and chemotherapeutic use in breast cancer treatment.
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