ABSTRACT
Cervical cancer is a worldwide public health problem, and improved selective therapies and anticancer drugs are urgently needed. In recent years, emodin has attracted considerable attention due to its anti-inflammatory, antineoplastic, and proapoptotic effects. Furthermore, emodin may be used as a photosensitizing agent in photodynamic therapy. Interest in photodynamic therapy for cancer treatment has increased due to its efficiency in causing tumor cell death. This study aimed to analyze the effect of emodin combined with photodynamic therapy in cervical carcinoma cell lines. At first, emodin presented cytotoxicity in concentration and time-dependent manners in all the specific cell lines analyzed. SiHa, CaSki, and HaCaT cancer cells presented more than 80% cell viability in concentrations below 30 µmol/L. Fluorescence microscopy images showed efficient cellular uptake of emodin in all analyzed cell lines. A significant decrease in cell viability was observed in SiHa, CaSki, and HaCaT cell lines after treatment of emodin combined with photodynamic therapy. These decreases were accompanied by increased ROS production, caspase-3 activity, and fluorescence intensity of autophagic vacuoles. This suggests increased ROS production led to cell death by apoptosis and autophagy. Additionally, after the combination of emodin and photodynamic therapy in SiHa cells, we observed the overexpression of 22 target genes and downregulation of two target genes of anti-cancer drugs. These results show the promising potential for applications that combine emodin with photodynamic therapy for cervical cancer treatment.
Subject(s)
Emodin , Photochemotherapy , Uterine Cervical Neoplasms , Apoptosis , Cell Line, Tumor , Emodin/pharmacology , Emodin/therapeutic use , Female , Humans , Photochemotherapy/methods , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Uterine Cervical Neoplasms/drug therapyABSTRACT
Infection with distinct Zika virus (ZIKV) strains in in vitro and in vivo models has demonstrated that the host's response to infection is strain-dependent. There has been no analysis of the impact of infection with different ZIKV strains on miRNA expression in human cells. We investigated miRNA expression in PNT1A cells upon infection with an African ZIKV strain (MR766) and a Brazilian ZIKV strain (ZIKVBR) using PCR array. Sixteen miRNAs were modulated in PNT1A cells: six miRNAs were modulated by both strains, while a set of ten miRNAs were modulated exclusively by ZIKVBR infection. In silico analysis showed that nine significant KEGG pathways and eight significant GO terms were predicted to be enriched upon ZIKVBR infection, and these pathways were related to cancer, environmental information processing, metabolism, and extracellular matrix. Differential modulation of miRNA expression suggests that distinct strains of ZIKV can differentially modulate the host response through the action of miRNAs.
Subject(s)
Gene Expression Regulation/immunology , MicroRNAs/metabolism , Zika Virus/classification , Animals , Chlorocebus aethiops , Epithelial Cells/metabolism , Epithelial Cells/virology , Gene Regulatory Networks , Humans , MicroRNAs/genetics , Vero CellsABSTRACT
Curcumin, a natural compound has several antineoplastic activities and is a promising natural photosensitizer used in photodynamic therapy. However, its low solubility in physiological medium limit the clinical use of curcumin. This study aimed to analyze the action of curcumin-nanoemulsion, a new and well-designed Drug Delivery System (DDS+) molecule, used as a photosensitizing agent in photodynamic therapy in an in vitro breast cancer model, MCF-7 cells. The empty nanoemulsion fulfils all necessary requirements to be an excellent DDS. Furthermore, the use of curcumin-nanoemulsion in photodynamic therapy resulted in a high phototoxic effect after activation at 440â¯nm, decreasing to <10% viable tumor cells after two irradiations and increasing the reactive oxygen species (ROS) production. The use of curcumin-nanoemulsion associated with photodynamic therapy resulted in an increase in the levels of caspase 3/7 activity for the studied MCF-7 cell model, indicating that this therapy triggers a cascade of events that lead to cell death, such as cellular apoptosis. In conclusion, curcumin-nanoemulsion proved to be efficient as a photosensitizing agent, had phototoxic effects, significantly decreased the proliferation of MCF-7 cells and stimulating the ROS production in combination with photodynamic therapy, so, this formulation has a great potential for use in treatment of breast cancer.
Subject(s)
Curcumin/chemistry , Nanostructures/chemistry , Photosensitizing Agents/chemistry , Apoptosis/drug effects , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Caspase 3/metabolism , Caspase 7 , Cell Proliferation/drug effects , Curcumin/pharmacology , Curcumin/therapeutic use , Female , Humans , Light , MCF-7 Cells , Particle Size , Photochemotherapy , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Reactive Oxygen Species/metabolismABSTRACT
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.
