Targeted delivery of chemotherapeutics in order to overcome side effects and enhance chemosensitivity remains a major issue in cancer research. In this context, biocompatible oil-in-water (O/W) microemulsions were developed as matrices for the encapsulation of DPS-2 a benzothiophene analogue, exhibiting high cytotoxicity in various cancer cell lines, among them the MW 164 skin melanoma and Caco-2 human epithelial colorectal adenocarcinoma cell lines. The microemulsion delivery system was structurally characterized by dynamic light scattering (DLS) and electron paramagnetic resonance (EPR) spectroscopy. The effective release of a lipophilic encapsulated compound was evaluated via confocal microscopy. The cytotoxic effect, in the presence and absence of DPS-2, was examined through the thiazolyl blue tetrazolium bromide (MTT) cell proliferation assay. When encapsulated, DPS-2 was as cytotoxic as when dissolved in dimethyl sulfoxide (DMSO). Hence, the oil cores of O/W microemulsions were proven effective biocompatible carriers of lipophilic bioactive molecules in biological assessment experiments. Further investigation through fluorescence-activated cell sorting (FACS) analysis, comet assay, and Western blotting, revealed that DPS-2, although non-genotoxic, induced S phase delay accompanied by cdc25A degradation and a nonapoptotic cell death in both cell lines, which implies that this benzothiophene analogue is a deoxyribonucleic acid (DNA) replication inhibitor.
Development of novel bioactive compounds against KRAS and/or BRAF mutant colorectal cancer (CRC) is currently an urgent need in oncology. In addition, single or multitarget kinase inhibitors against MEK/ERK and PI3K/AKT pathways are of potential therapeutic advantage. A new compound based on the benzothiophene nucleus was synthesized, based on previous important outcomes on other pharmaceutical preparations, to be tested as potential anticancer agent. Treatments by 2-5 μM DPS-2 of several CRC and melanoma cell lines bearing either BRAF or KRAS mutations have shown a remarkable effect on cell viability in 2D and 3D cultures. More detailed analysis has shown that DPS-2 can kill cancer cells by apoptosis, reducing at the same time their autophagy properties. After testing activities of several signaling pathways, the compound was found to have a dual inhibition of two major proliferative/survival pathways, MEK/ERK and PI3K/AKT, in both CRC and melanoma, thus providing a mechanistic evidence for its potent anticancer activity. Antitumor activity of DPS-2 was further validated in vivo , as DPS-2 treatment of mouse xenografts of Colo-205 colorectal cancer cells remarkably reduced their tumor formation properties. Our findings suggest that DPS-2 has significant anti-KRAS/ anti-BRAF mutant CRC activity in preclinical models, potentially providing a novel treatment strategy for these difficult-to-treat tumors, which needs to be further exploited.
The sample preparation of a cosmetic specimen in Cosmetic Science for the purpose of determining the analytical composition of heavy and toxic metals such as lead (Pb), mercury (Hg), cadmium (Cd), and arsenic (As) is of particular importance due to the difficulty of handling the sample. There are two main methods of sample preparation. The first method is the wet digestion of the sample with strong acids such as H2SO4, HNO3, HF, and HNO3/HCl (1:3) and the combination of a strong acid with H2O2. Liquid digestion of the sample under the influence of strong acids damages the organic material of the sample and converts the carbon into carbon dioxide. The contained metals are oxidized to the highest oxidizing step and converted to soluble salts. A problem with this method is the loss of metals during digestion because it occurs at high temperatures as well as the decrease in the concentration of the residual acid. The second method of preparation is the wet liquid digestion of the sample with strong acids in a microwave oven in a closed vessel. The acids that are used are mainly HNO3 or mixtures of acids such as HNO3–HCl and HNO3–H2SO4. When the sample in the acid’s solvent is exposed to microwave energy, it can reach temperatures substantially above the boiling temperature of the acid solution. The result is the decomposition of the organic material, the oxidation of the metals, and their conversion to soluble nitrates. The advantages of using microwaves are the ability to control the temperature, pressure, and loss of metals and, thus, avoid erroneous measurement results. Simultaneously with the above, extraction methods have been, for almost a decade, very effective complementary processes that we can use to enrich a sample of a cosmetic product. Liquid–liquid dispersion micro-extraction (DLLME) and solid phase extraction (SPE) are the two main methods used in sample preparation and are usually applied after the digestion process.
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