The growing interest of oncologists in natural compounds such as polyphenols and flavonoids is encouraging the development of innovative and efficient carriers for the delivery of those drugs. This study examines carboxymethyl chitosan-based microcapsules created by spray drying as a method for delivering biologically active compounds isolated from the Cistus herb. Effects of sterilization and encapsulation on the polyphenol and flavonoid content of Cistus extract were investigated to optimize the production process. Furthermore, in vitro studies were carried out to examine the anticancer properties of sterilized polyphenols and flavonoids on glioblastoma cells isolated from oncological patients. Acquired results show high anticancer potential towards glioblastoma as well as low cytotoxicity towards non-cancer cell lines by the substances in question. Steam sterilization is shown to affect the content of biologically active compounds the least. We demonstrate that the investigated form of drug encapsulation is both efficient and potentially possible to scale up from the viewpoint of the pharmaceutical industry.

In 2016, the WHO introduced new guidelines for the diagnosis of brain gliomas based on new genomic markers. The addition of these new markers to the pre-existing diagnostic methods provided a new level of precision for the diagnosis of glioma and the prediction of treatment effectiveness. Yet, despite this new classification tool, glioblastoma (GBM), a grade IV glioma, continues to have one of the highest mortality rates among central nervous system tumors. Metabolomics is a particularly promising tool for the analysis of GBM tumors and potential methods of treating them, as it is the only “omics” approach that is capable of providing a metabolic signature of a tumor’s phenotype. With careful experimental design, cell cultures can be a useful matrix in GBM metabolomics, as they ensure stable conditions and, under proper conditions, are capable of capturing different tumor phenotypes. This paper reviews in vitro metabolomic profiling studies of high-grade gliomas, with a particular focus on sample-preparation techniques, crucial metabolites identified, cell culture conditions, in vitro-in vivo extrapolation, and pharmacometabolomics. Ultimately, this review aims to elucidate potential future directions for in vitro GBM metabolomics.

Volatile organic compounds (VOCs) have been proposed in the last two decades as biomarkers for disease detection and therapeutic monitoring. Model in vitro experiments with established cell lines are fundamental to clarify whether given VOCs originate from normal human cells or pathogens, including transformed cancer cells. Due to the trace concentrations of target metabolites, adsorptive enrichment is needed before gas chromatography-mass spectrometry (GC-MS) analysis, with solid-phase microextraction (SPME) being perfectly suited for this purpose. Here, a modification of SPME, the thin-film microextraction (TFME) technique, is proposed for analysis of cellular VOCs, which utilizes a planar mesh coated with stationary phase to increase the extraction phase volume and active surface area. In this study, four different adsorbents were compared: carboxen, divinylbenzene, hydrophobic−lipophilic balanced and polydimethylsiloxane. Amongst them, HLB sheets using poly(divinylbenzene-co-N-vinyl-pyrrolidone) skeleton structure proved to be the most versatile, enabling the most sensitive analysis of VOCs with a broad polarity and volatility. For HLB, sampling type (internal static headspace, external bi-directional headspace), extraction temperature and extraction time were also examined. An established method was successfully applied to analyze metabolites produced by A549 cells revealing five volatiles at significantly higher (additionally benzaldehyde at lower) levels in cell culture medium compared to the cell-free reference medium headspace.

The presented study depicts the synthesis of 11 carborane–thiazole conjugates with anticancer activity, as well as an evaluation of their biological activity as inhibitors of two enzymes: tyrosinase and 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). The overexpression of tyrosinase results in the intracellular accumulation of melanin and can be observed in melanoma. The overexpression of 11β-HSD1 results in an elevation of glucocorticoid levels and has been associated with the aggravation of metabolic disorders such as type II diabetes mellitus and obesity. Recently, as the comorbidity of melanomas and metabolic disorders is being recognized as an important issue, the search for new therapeutic options has intensified. This study demonstrates that carborane–thiazole derivatives inhibit both enzymes, exerting beneficial effects. The antiproliferative action of all newly synthesized compounds was evaluated using three cancer cell lines, namely A172 (human brain glioblastoma), B16F10 (murine melanoma) and MDA-MB-231 (human breast adenocarcinoma), as well as a healthy control cell line of HUVEC (human umbilical vein endothelial cells). The results show that 9 out of 11 newly synthesized compounds demonstrated similar antiproliferative action against the B16F10 cell line to the reference drug, and three of these compounds surpassed it. To the best of our knowledge, this study is the first to demonstrate dual inhibitory action of carborane–thiazole derivatives against both tyrosinase and 11β-HSD1. Therefore, it represents the first step towards the simultaneous treatment of melanoma and comorbid diseases such as type II diabetes mellitus.

Gallium maltolate (GaM) targets iron-dependent processes in glioblastoma (GBM), but responses vary with model context. We evaluated GaM across established (A-172, U-87 MG) and patient-derived (3005, 3019, 3034, 3048, 3073) GBM lines in 2D and 3D using viability modelling (IC10/IC50/IC90), TFRC quantification, oxygen consumption rate (OCR), and PCA/PLS-DA– guided metabolomics with FDR and VIP-based selection. GaM reduced viability in all models, with a right-shift of dose–response in 3D. TFRC correlated with IC50 in 2D but not 3D, unless excluding U-87 MG from the analysis. OCR was markedly suppressed in A-172, U-87 MG, 3048, and 3073, particularly in 3D, while 3005 and 3019 were more respiration-resilient. Multivariate analyses showed treatment-dominant separation in 3005/3048, format dominance in 3019/3034, and time effects in A-172/U-87 MG/3073. A concise metabolic signature (tryptophan, methionine, uracil, allantoin) indicated coordinated perturbations in amino acid, nucleotide, and redox pathways. These findings support 3D, patient-derived systems for more predictive GaM evaluation.