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The interpretation of the biochemistry of immune metabolism could be considered an attractive scientific field of biomedicine research. In this review, the role of glycolysis in macrophage polarization is discussed together with mitochondrial metabolism in cancer cells. In the first part, the focus is on the Warburg effect and redox metabolism during macrophage polarization, cancer development, and management of the immune response by the cancer cells. The second part addresses the possibility of impacts on the Warburg effect through targeting peroxisome proliferator-activated receptors (PPARs). This could be an activator of native immune responses. Because of the reported serious adverse effects of using synthetic ligands for PPARs in combination with chemotherapeutics, searches for less toxic and more active PPAR inhibitors, as well as blocking undesirable cellular PPAR-dependent processes, are in progress. On the other hand, recent research in modern immunotherapy has focused on the search for gentle immune-modulating natural compounds with harmless synergistic chemotherapeutic efficacy that can be used as an adjuvant. It is a well-known fact that the plant kingdom is a source of important therapeutic agents with multifaceted effectiveness. One of these is the known association with PPAR activities. In this regard, the secondary metabolites extracted from plants could change the game.

Several phytochemicals, which display antioxidant activity and inhibit cancer cell phenotypes, could be used for cancer treatment and prevention. Lignin, as a part of plant biomass, is the second most abundant natural biopolymer worldwide, and represents approximately 30% of the total organic carbon content of the biosphere. Historically, lignin-based products have been viewed as waste materials of limited industrial usefulness, but modern technologies highlight the applicability of lignin in a variety of industrial branches, including biomedicine. The aims of our preliminary study were to compare the antioxidant properties of water-soluble alkali lignin solutions, before and after UV-B irradiation, as well as to clarify their effect on colon cancer cell viability (Colon 26), applied at low (tolerable) concentrations. The results showed a high antioxidant capacity of lignin solutions, compared to a water-soluble control antioxidant standard (Trolox) and remarkable radical scavenging activity was observed after their UV-B irradiation. Diminishment of cell viability as well as inhibition of the proliferative activity of the colon cancer cell line with an increase in alkali lignin concentrations were observed. Our results confirmed that, due to its biodegradable and biocompatible nature, lignin could be a potential agent for cancer therapy, especially in nanomedicine as a drug delivery system., Competing Interests: The authors declare no conflicts of interest.

Our study proposes a pharmacological strategy to target cancerous mitochondria via redox-cycling "mitocans" such as quinone/ascorbate (Q/A) redox-pairs, which makes cancer cells fragile and sensitive without adverse effects on normal cells and tissues. Eleven Q/A redox-pairs were tested on cultured cells and cancer-bearing mice. The following parameters were analyzed: cell proliferation/viability, mitochondrial superoxide, steady-state ATP, tissue redox-state, tumor-associated NADH oxidase (tNOX) expression, tumor growth, and survival. Q/A redox-pairs containing unprenylated quinones exhibited strong dose-dependent antiproliferative and cytotoxic effects on cancer cells, accompanied by overproduction of mitochondrial superoxide and accelerated ATP depletion. In normal cells, the same redox-pairs did not significantly affect the viability and energy homeostasis, but induced mild mitochondrial oxidative stress, which is well tolerated. Benzoquinone/ascorbate redox-pairs were more effective than naphthoquinone/ascorbate, with coenzyme Q0/ascorbate exhibiting the most pronounced anticancer effects in vitro and in vivo. Targeted anticancer effects of Q/A redox-pairs and their tolerance to normal cells and tissues are attributed to: (i) downregulation of quinone prenylation in cancer, leading to increased mitochondrial production of semiquinone and, consequently, superoxide; (ii) specific and accelerated redox-cycling of unprenylated quinones and ascorbate mainly in the impaired cancerous mitochondria due to their redox imbalance; and (iii) downregulation of tNOX.

The aim of the present study was to synthesize lignin microparticles, to evaluate their physicochemical, spectral, morphological and structural characteristics, to examine their encapsulation and in vitro release potential and behaviour towards the flavonoid morin in simulated physiological medium and to assess the in vitro radical-scavenging potential of the morin-loaded lignin microcarrier systems. The physicochemical, structural and morphological characteristics of alkali lignin, lignin particles (LP) and morin-encapsulated lignin microparticles (LMP) were determined based on particle size distribution, SEM, UV/Vis spectrophotometric, FTIR and potentiometric titration analyses. The encapsulation efficiency of LMP was 98.1%. The FTIR analyses proved that morin was successfully encapsulated in the LP without unexpected chemical reactions between the flavonoid and the heteropolymer. The in vitro release performance of the microcarrier system was successfully mathematically described by Korsmeyer-Peppas and the sigmoidal models outlining the general role of diffusion during the initial stages of the in vitro release process in simulated gastric fluid (SGF), and the predominant contribution of biopolymer relaxation and erosion was determined in simulated intestinal medium (SIF). The higher radical-scavenging potential of LMP, as compared to that of LP, was proven via DPPH and ABTS assays. The synthesis of lignin microcarriers not only provides a facile approach for the utilization of the heteropolymer but also determines its potential for the design of drug-delivery matrices.

Isolation and characterization of new biologically active substances affecting cancer cells is an important issue of fundamental research in biomedicine. Trehalose lipid was isolated from Rhodococcus wratislav i ensis strain and purified by liquid chromatography. The effect of trehalose lipid on cell viability and migration, together with colony forming assays, were performed on two breast cancer (MCF7-low metastatic; MDA-MB231-high metastatic) and one "normal" (MCF10A) cell lines. Molecular modeling that details the structure of the neutral and anionic form (more stable at physiological pH) of the tetraester was carried out. The tentative sizes of the hydrophilic (7.5 Å) and hydrophobic (12.5 Å) portions of the molecule were also determined. Thus, the used trehalose lipid is supposed to interact as a single molecule. The changes in morphology, adhesion, viability, migration, and the possibility of forming colonies in cancer cell lines induced after treatment with trehalose lipid were found to be dose and time dependent. Based on the theoretical calculations, a possible mechanism of action and membrane asymmetry between outer and inner monolayers of the bilayer resulting in endosome formation were suggested. Initial data suggest a mechanism of antitumor activity of the purified trehalose lipid and its potential for biomedical application., Competing Interests: The authors declare no conflict of interest.