RESUMEN
Cervical carcinoma is the most common gynecological cancer among young and adult women. There has been increasing interest in natural sources for cervical carcinoma treatment, especially for active compounds from plant extracts as antineoplastic agents. Berberine is an example of one these promising natural products. It is a natural isoquinoline alkaloid and comes from plants, such as Berbis, Coptis, and Hydrastis. It is widely used in Chinese medicine and has demonstrated activity against various cancer cell lines. This work aims to analyze the efficiency of berberine-containing nanoemulsions as photosensitizing agents in photodynamic therapy and their interaction with cervical carcinoma cells and immortalized human keratinocyte cell line. Among all groups tested, berberine nanoemulsions combined with photodynamic therapy induced the most statistically significant phototoxicity in the evaluated cell lines. Fluorescence microscopy demonstrated that the compound was present for up to 48 h when berberine nanoemulsions were used. The reactive oxygen species assay showed an increase in reactive oxygen species in the two studied cell lines after treatment of berberine-containing nanoemulsion combined with photodynamic therapy. The autophagy trial showed significant increases in cell death when berberine-containing nanoemulsion treatment was combined with photodynamic therapy when compared to trichostatin A treatment as a positive control. However, caspase-3 activity did not significantly increase in cervical carcinoma cells and immortalized human keratinocyte cell line. The results suggest that nanoemulsions with berberine have potential for use as photosensitizing agents in photodynamic therapy to treat cervical carcinoma.
Asunto(s)
Berberina , Carcinoma , Fotoquimioterapia , Adulto , Apoptosis , Berberina/farmacología , Línea Celular Tumoral , Femenino , Humanos , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/farmacologíaRESUMEN
Renal cell carcinoma (RCC) consists of the most lethal common urological cancer and the clinical practice has shown that resistant RCC to commons therapies is extremely high. Berberine is an isoquinoline alkaloid, presents in different kinds of plants and it has long been used in Chinese medicine. It has several properties, such as antioxidant, anti-inflammatory, anti-diabetic, anti-microbial and anti-cancer. Moreover, berberine has photosensitive characteristics and its association with photodynamic therapy (PDT) is effective against tumor cells. This study aimed to evaluate the effects of berberine associated with PDT in renal carcinoma cell lines. The cellular viability assay showed increased cytotoxicity in concentration and time-dependent manner. Berberine presented efficient internalization in all cell lines analyzed. In addition, after treatment with berberine associated with PDT, it was observed a high phototoxicity effect with less than 20 % of viable cells. In this study we observed that the increase of reactive oxygen species (ROS) levels was accompanied by an increase of autophagy levels and apoptosis by caspase 3 activity, suggesting cell death by both mechanisms. Additionally, three target genes of anti-cancer drugs were differentially expressed in 786-O cells, being that Vascular Endothelial Growth Factor-D (FIGF) and Human Telomerase Reverse Transcriptase (TERT) gene presented low expression and Polo Like Kinase 3 (PLK3) presented overexpression after treatment with berberine associated with PDT. In this study, the proposed treatment triggered metabolites changes related to cell proliferation, tumorigenesis and angiogenesis. Thus, it was possible to suggest that berberine has promising potential as a photosensitizing agent in a photodynamic therapy, because it induced significant anticancer effects on renal carcinoma cells.
Asunto(s)
Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Berberina/farmacología , Carcinoma de Células Renales/patología , Neoplasias Renales/patología , Fotoquimioterapia , Especies Reactivas de Oxígeno/metabolismo , Berberina/toxicidad , Carcinoma de Células Renales/genética , Caspasa 3/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Neoplasias Renales/genética , Metaboloma , Espectroscopía de Protones por Resonancia MagnéticaRESUMEN
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.