Pathways Related to the Anti-Cancer Effects of Metabolites Derived from Cerrado Biome Native Plants: An Update and Bioinformatics Analysis on Oral Squamous Cell Carcinoma.

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.

Enhanced surface plasmon resonance (SPR) signals based on immobilization of core-shell nanoparticles incorporated boron nitride nanosheets: Development of molecularly imprinted SPR nanosensor for anticancer drug, etoposide.

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 0.001-1.00 ng mL-1 (1.70 × 10-12-1.70 × 10-9 M) and 0.00025 ng mL-1 (4.25 × 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.

Sesquiterpenoids and flavonoids from the aerial parts of Tithonia diversifolia and their cytotoxic activity.

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.

Separation of selected anticancer drugs using superheated water as the mobile phase.

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.

Separation of etoposide phosphate and methotrexate by capillary zone electrophoresis using UV detection with a high sensitivity cell.

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.

Ultrafiltration and subsequent high performance liquid chromatography for in vivo determinations of the protein binding of etoposide.

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.

Concentration- and time-dependent cytostatic effects of methotrexate and etoposide on L1210 leukemic cells in vitro demonstrated by a new microperfusion method.

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.

VP-16-213 (etoposide): the mandrake root from Issyk-Kul.

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.

Analysis of the anticancer drugs VP 16-213 and VM 26 and their metabolites by high-performance liquid chromatography.

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.