RESUMEN
BACKGROUND: Oral cancer is a significant health problem worldwide. Oral squamous cell carcinoma (OSCC) is a malignant neoplasm of epithelial cells that mostly affects different anatomical sites in the head and neck and derives from the squamous epithelium or displays similar morphological characteristics. Generally, OSCC is often the end stage of several changes in the stratified squamous epithelium, which begin as epithelial dysplasia and progress by breaking the basement membrane and invading adjacent tissues. Several plant-based drugs with potent anti-cancer effects are considered inexpensive treatments with limited side effects for cancer and other diseases. OBJECTIVE: The aim of this review is to explore whether some Brazilian plant extracts or constituents exhibit anti-tumorigenic activity or have a cytotoxic effect on human oral carcinoma cells. METHODS: Briefly, OSCC and several metabolites derived from Brazilian plants (i.e., flavonoids, vinblastine, irinotecan, etoposide and paclitaxel) were used as keywords to search the literature on PubMed, GenBank and GeneCards. RESULTS: The results showed that these five chemical compounds found in Cerrado Biome plants exhibit anti-neoplastic effects. Evaluating the compounds revealed that they play a main role in the regulation of cell proliferation. CONCLUSION: Preserving and utilising the biodiversity of our planet, especially in unique ecosystems, such as the Cerrado Biome, may prove essential to preserving and promoting human health in modern contexts.
Asunto(s)
Anticarcinógenos/farmacología , Antineoplásicos Fitogénicos/farmacología , Carcinogénesis/efectos de los fármacos , Carcinoma de Células Escamosas/tratamiento farmacológico , Neoplasias de la Boca/tratamiento farmacológico , Proteínas de Neoplasias/genética , Anticarcinógenos/química , Anticarcinógenos/aislamiento & purificación , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Brasil , Carcinogénesis/genética , Carcinogénesis/metabolismo , Carcinogénesis/patología , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Proliferación Celular/efectos de los fármacos , Biología Computacional/métodos , Etopósido/química , Etopósido/aislamiento & purificación , Etopósido/farmacología , Flavonoides/química , Flavonoides/aislamiento & purificación , Flavonoides/farmacología , Regulación Neoplásica de la Expresión Génica , Humanos , Irinotecán/química , Irinotecán/aislamiento & purificación , Irinotecán/farmacología , Neoplasias de la Boca/genética , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/patología , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/metabolismo , Paclitaxel/química , Paclitaxel/aislamiento & purificación , Paclitaxel/farmacología , Extractos Vegetales/química , Plantas Medicinales , Vinblastina/química , Vinblastina/aislamiento & purificación , Vinblastina/farmacologíaRESUMEN
An effective SPR nanosensor based on core-shell nanoparticles (Ag@AuNPs) incorporated hexagonal boron nitride (HBN) nanosheets and molecularly imprinted polymer (MIP) was presented for etoposide (ETO) detection. Scanning electron microscope (SEM), transmission electron microscope (TEM), x-ray diffraction (XRD) method, cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), fourier transform infrared (FTIR) spectroscopy and atomic force microscopy (AFM) methods were utilized for all characterizations of nanomaterials and polymer surfaces. ETO imprinted SPR nanosensor based on Ag@AuNPs-HBN nanocomposite was developed in the presence of poly(2-hydroxyethyl methacrylate-methacryloylamidoglutamic acid) [p(HEMA-MAGA)]. The results of the study have revealed that 0.001-1.00â¯ngâ¯mL-1 (1.70â¯×â¯10-12-1.70â¯×â¯10-9 M) and 0.00025â¯ngâ¯mL-1 (4.25â¯×â¯10-13 M) were found as the linearity range and the detection limit (LOD). Furthermore, the prepared SPR nanosensor was examined in terms of stability, repeatability and selectivity. Finally, the imprinted SPR nanosensor was applied to the urine samples having high recovery.
Asunto(s)
Antineoplásicos/aislamiento & purificación , Técnicas Biosensibles , Etopósido/aislamiento & purificación , Nanopartículas del Metal/química , Antineoplásicos/química , Compuestos de Boro/química , Espectroscopía Dieléctrica , Etopósido/química , Etopósido/uso terapéutico , Oro/química , Humanos , Impresión Molecular , Neoplasias/tratamiento farmacológico , Polímeros/química , Espectroscopía Infrarroja por Transformada de Fourier , Resonancia por Plasmón de SuperficieRESUMEN
Cytotoxicity-guided fractionation of the 80% EtOH extract of Tithonia diversifolia has resulted in the isolation of twelve sesquiterpenoids (1-12), including three new ones (4, 10, 12), and three known flavonoids (13-15). The structures of the new compounds were determined by analysis of their spectroscopic data. The isolated compounds showed cytotoxic activity against HL-60 leukemia cells with IC(50) values ranging from 0.13 to 13.0 microM, when etoposide used as a positive control gave an IC(50) value of 0.43 microM. The cancer growth inhibitory property of 9, the main cytotoxic compound in T. diversifolia, was examined using a disease-oriented panel composed of 39 human cancer cell lines in the Japanese Foundation for Cancer Research.
Asunto(s)
Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Asteraceae/química , Flavonoides/química , Flavonoides/farmacología , Sesquiterpenos/química , Sesquiterpenos/farmacología , Antineoplásicos Fitogénicos/aislamiento & purificación , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Etanol , Etopósido/química , Etopósido/aislamiento & purificación , Flavonoides/aislamiento & purificación , Células HL-60 , Humanos , Extractos Vegetales , Sesquiterpenos/aislamiento & purificación , Solventes , Espectrometría de Masa por Ionización de Electrospray , Espectrofotometría Infrarroja , Espectrofotometría UltravioletaRESUMEN
Six anticancer drugs have been eluted on a polystyrene-divinylbenzene (PS-DVB) column with buffered superheated water as the mobile phase. The temperature range studied was from ambient temperature up to 160 degrees C, and the pH of the water was adjusted to 11.5 and 3.5 with phosphate buffer. It was possible to separate the substances 5-fluorouracil (5-FU), methotrexate (MTX), 7-hydroxymethotrexate (7-OH-MTX), and etoposide (VP-16) in one chromatographic run. The separation of these substances was optimized when adjusting the pH from 11.5 to 3.5, resulting in a total elution time of less than 13 min. Furthermore, retention factors of all of the investigated substances were measured at different temperatures and pH values.
Asunto(s)
Antineoplásicos/aislamiento & purificación , Etopósido/aislamiento & purificación , Fluorouracilo/aislamiento & purificación , Calor , Metotrexato/aislamiento & purificación , Agua/química , Metotrexato/análogos & derivadosRESUMEN
Etoposide phosphate and methotrexate are important anti-tumor chemotherapeutic agents. Our previously presented capillary zone electrophoresis (CZE) method using a high sensitivity cell (Z-cell) for quantitative analysis in biological media (urine, plasma) showed good precision and accuracy. The present results show that the investigation using a capillary with high sensitivity cell led to an approximately 10-fold improvement of the detection limit compared to standard capillaries. Plasma and urine samples were analyzed by using a calibration curve for drug concentrations between 0.1 and 100 microg/mL. Good detection limits and good relative standard deviations of the migration times and of the peak areas were observed in these experiments.
Asunto(s)
Antineoplásicos/aislamiento & purificación , Etopósido/análogos & derivados , Metotrexato/aislamiento & purificación , Compuestos Organofosforados/aislamiento & purificación , Antineoplásicos/sangre , Antineoplásicos/orina , Electroforesis Capilar , Etopósido/sangre , Etopósido/aislamiento & purificación , Etopósido/orina , Femenino , Humanos , Metotrexato/sangre , Metotrexato/orina , Compuestos Organofosforados/sangre , Compuestos Organofosforados/orinaRESUMEN
Etoposide is extensively (approximately 94%) bound to plasma proteins and the free non-protein-bound levels have been shown to correlate more closely to toxicity than total drug concentrations. A rapid and easily performed method, compared to the time consuming equilibrium dialysis, to obtain the free fraction is needed. The aim of this study was to evaluate ultrafiltration and subsequent high performance liquid chromatography (HPLC) for the determination of protein binding of etoposide. Spiked plasma from healthy, drug-free volunteers was used to compare ultrafiltration, using Amicon Centrifree filters, with equilibrium dialysis at 37 degrees C. The variability (CV) of the ultrafiltration method was 6.1 and 13.5% (n = 6) at 37 degrees C and room temperature (RT), respectively. The relative size of the free fraction obtained by ultrafiltration at 37 degrees C and RT was 1.22 (P = 0.0005) and 0.37 (P = 0.0001), respectively, compared with equilibrium dialysis at 37 degrees C. The chromatographic separation of metabolites from the mother compound when free etoposide is analyzed is crucial. It is shown that a hydroxy-acid metabolite of etoposide is quite dominant in a protein-free plasma fraction. The free concentrations were determined throughout a dose interval of 24 h in a patient receiving etoposide 100 mg/m2 daily. Ultrafiltration and subsequent HPLC is considered convenient and suitable for in vivo pharmacokinetic investigations.
Asunto(s)
Proteínas Sanguíneas/metabolismo , Etopósido/sangre , Antineoplásicos/sangre , Antineoplásicos/aislamiento & purificación , Antineoplásicos/uso terapéutico , Proteínas Sanguíneas/aislamiento & purificación , Cromatografía Líquida de Alta Presión/métodos , Diálisis/métodos , Etopósido/aislamiento & purificación , Etopósido/uso terapéutico , Humanos , Leucemia Mieloide Aguda/sangre , Leucemia Mieloide Aguda/tratamiento farmacológico , Valores de Referencia , Tenipósido/sangre , Tenipósido/aislamiento & purificación , Ultrafiltración/métodosRESUMEN
For validation of a new microperfusion system to follow the influence of pharmacokinetic parameters of cytostatic drugs on cultured tumor cells, we investigated the effects of methotrexate (MTX) and etoposide (VP16-213) on L1210 colony growth. Inhibition kinetics of cells were compared to those obtained by suspension culture exposure. We found good correlations between the IC50 values measured with either method. Evaluation of the kinetics under constant drug concentrations (steady-state) showed that the microperfusion method is comparable to other methods. A simple HPLC column-switching method was developed to determine drug concentrations in serum-free medium. Under these conditions solutions of etoposide were found to be unstable. Its quantity decreased biphasically with a concentration-dependent first-order kinetic in the initial phase. The relevance of exposure dose (cxt) for the mode of drug action has been shown, especially for instable solutions of drugs (VP16-213). The microperfusion method might substantially improve in vitro screening assays of anticancer drugs.
Asunto(s)
Etopósido/farmacología , Etopósido/farmacocinética , Leucemia L1210/tratamiento farmacológico , Leucemia L1210/metabolismo , Metotrexato/farmacología , Metotrexato/farmacocinética , Animales , Cromatografía , Estabilidad de Medicamentos , Etopósido/aislamiento & purificación , Cinética , Metotrexato/aislamiento & purificación , Ratones , Microquímica/métodos , Perfusión , Células Tumorales CultivadasRESUMEN
VP-16-213 (etoposide) is an orally and parenterally active antineoplastic agent synthesized from podophyllum extracts of a common North American plant, the May apple or mandrake. The drug delays and kills cells in the G2 phase of the cell cycle and is active in a variety of animal tumors and leukemias. Major therapeutic activity for the drug has been found in small cell bronchogenic carcinoma, germ cell malignancies, acute non-lymphocytic leukemia, Hodgkin's disease and non-HOdgkin's lymphoma. Minor therapeutic activity of the drug occurs in non-small cell bronchogenic carcinoma, pediatric neoplasms, hepatocellular carcinoma and gastric cancer. Toxicity is primarily hematologic, with alopecia, nausea and vomiting occurring less frequently.
Asunto(s)
Etopósido/uso terapéutico , Podofilotoxina/análogos & derivados , Animales , Neoplasias de la Mama/tratamiento farmacológico , Carcinoma de Células Pequeñas/tratamiento farmacológico , Ciclo Celular/efectos de los fármacos , Fenómenos Químicos , Química , Ensayos Clínicos como Asunto , Disgerminoma/tratamiento farmacológico , Etopósido/aislamiento & purificación , Etopósido/farmacología , Femenino , Humanos , Leucemia/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Linfoma/tratamiento farmacológico , RatonesRESUMEN
A rapid and convenient high-performance liquid chromatographic procedure for the analysis of the clinically useful anticancer agents VP 16-213 and VM 26 is described. The drugs, which are semi-synthetic derivatives of the natural product podophyllotoxin, are extracted from plasma with chloroform. The extracts are evaporated to dryness, reconstituted in methanol, and chromatographed on a reversed-phase microparticle C18 column using isocratic elution with a mixture of methanol--water (60:40). Each drug is used as the internal standard for the other. Quantitation to 500 ng/ml (0.85 nmole/ml) plasma is based on peak height ratios using UV detection at 254 nm. Patient plasma concentration versus time data agree well with previously published data obtained using radiolabelled drug. Investigations into the nature of the hydroxy acid metabolite of VP 16-213, carried out using paired-ion chromatography with tetrabutylammonium bromide and fluorescence detection, are described. Also, a unique separation of VP 16-213 and a possible metabolite, the isomer, picro VP 16-213, is described.