RESUMEN
In this article, rapid one pot synthesis of gold nanoparticles (GNPs) using an eco-friendly extract of Genipa americana L. fruit is described. Electrospray ionization mass spectrometry (ESI-MS) and Fourier transform infrared (FTIR) spectroscopic studies demonstrated that small molecules such as genipin, genipaol, geniposide and ranolazine can act as reducer as well as stabilizers. The monodispersed, spherical GNPs were further characterized by UV-vis spectroscopy at λmax=535 nm, transmission electron microscopy (TEM), dynamic light scattering (DLS) and X-ray diffraction (XRD) analysis. This synthetic approach offers a greener and alternate route to the preparation of GNPs free from toxic chemical components and stable for 6-7 months under room temperature. The green synthesized GNPs showed weak antioxidant efficacy against 1,1-diphenyl-2-picrylhydrazyl and no cytotoxicity against A-549 and HeLa human cancer cell lines, from lung and cervix. This study opens a new industrial scope of G. americana fruit in nanoscience and as surface modified GNPs can be developed into a successful drug carrier for future pharmaceutical products.
Asunto(s)
Oro/química , Nanopartículas del Metal/química , Rubiaceae/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Dispersión Dinámica de Luz , Frutas/química , Frutas/metabolismo , Tecnología Química Verde , Células HeLa , Humanos , Nanopartículas del Metal/toxicidad , Microscopía Electrónica de Transmisión , Extractos Vegetales/química , Rubiaceae/metabolismo , Espectrometría de Masa por Ionización de Electrospray , Espectrofotometría Ultravioleta , Espectroscopía Infrarroja por Transformada de Fourier , Difracción de Rayos XRESUMEN
Hepatocellular carcinoma (HCC) has very poor prognosis. Astemizole has gained great interest as a potential anticancer drug because it targets several proteins involved in cancer including the Eag1 (ether à-go-go-1) potassium channel that is overexpressed in human HCC. Eag1 channels are regulated by cancer etiological factors and have been proposed as early tumor markers. Here, we found that HepG2 and HuH-7 HCC cells displayed Eag1 messenger RNA (mRNA) and protein expression, determined by real-time RT-PCR and immunochemistry, respectively. Astemizole inhibited human HCC cell proliferation (assessed by metabolic activity assay) and induced apoptosis (studied with flow cytometry) in both cell lines. The subcellular Eag1 protein localization was modified by astemizole in the HepG2 cells. The treatment with astemizole prevented diethylnitrosamine (DEN)-induced rat HCC development in vivo (followed by studying γ-glutamyl transpeptidase (GGT) activity). The Eag1 mRNA and protein levels were increased in most DEN-treated groups but decreased after astemizole treatment. GGT activity was decreased by astemizole. The Eag1 protein was detected in cirrhotic and dysplastic rat livers. Astemizole might have clinical utility for HCC prevention and treatment, and Eag1 channels may be potential early HCC biomarkers. These data provide significant basis to include astemizole in HCC clinical trials.
Asunto(s)
Astemizol/administración & dosificación , Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/genética , Canales de Potasio Éter-A-Go-Go/biosíntesis , Neoplasias Hepáticas/genética , Animales , Apoptosis/efectos de los fármacos , Biomarcadores de Tumor/biosíntesis , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Proliferación Celular/efectos de los fármacos , Dietilnitrosamina/administración & dosificación , Canales de Potasio Éter-A-Go-Go/genética , Regulación Neoplásica de la Expresión Génica , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Estadificación de Neoplasias , Pronóstico , Ratas , gamma-Glutamiltransferasa/biosíntesisRESUMEN
OBJECTIVE: Cervical cancer is a major cause of mortality among women in developing countries. Thus, it is necessary to offer novel therapies to treat this malignancy. Astemizole has been suggested as a novel and interesting anticancer agent because it targets several proteins involved in cancer including Eag1 (ether à-go-go-1) potassium channels. Eag1 has been proposed as a tumor marker for different types of cancer. Actually, we previously suggested Eag1 channels as cervical cancer and dysplasia markers. Besides, Eag1 has been proposed as a therapeutic target for different malignancies. However, the effect of astemizole in cervical cancer cells is unknown. Therefore, we investigated the effect of astemizole on the proliferation and apoptosis of cervical cancer cells. METHODS: Five cervical cancer cell lines (HeLa, SiHa, CaSki, INBL, and C-33A) were cultured according to manufacturer's instructions. Eag1 protein expression was studied by immunocytochemistry. Cell proliferation was assayed with the MTT method, and apoptosis was investigated by flow cytometry. RESULTS: Eag1 protein expression was observed in different cell lines. Astemizole decreased cell proliferation in up to 40% and increased apoptosis severalfold in all the cell lines studied. CONCLUSIONS: Our results suggest astemizole as a potential therapy for cervical cancer.
