Glycolysis is a crucial metabolic process in rapidly proliferating cells such as cancer cells. Phosphofructokinase-1 (PFK-1) is a key rate-limiting enzyme of glycolysis. Its efficiency is allosterically regulated by numerous substances occurring in the cytoplasm. However, the most potent regulator of PFK-1 is fructose-2,6-bisphosphate (F-2,6-BP), the level of which is strongly associated with 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase activity (PFK-2/FBPase-2, PFKFB). PFK-2/FBPase-2 is a bifunctional enzyme responsible for F-2,6-BP synthesis and degradation. Four isozymes of PFKFB (PFKFB1, PFKFB2, PFKFB3, and PFKFB4) have been identified. Alterations in the levels of all PFK-2/FBPase-2 isozymes have been reported in different diseases. However, most recent studies have focused on an increased expression of PFKFB3 and PFKFB4 in cancer tissues and their role in carcinogenesis. In this review, we summarize our current knowledge on all PFKFB genes and protein structures, and emphasize important differences between the isoenzymes, which likely affect their kinase/phosphatase activities. The main focus is on the latest reports in this field of cancer research, and in particular the impact of PFKFB3 and PFKFB4 on tumor progression, metastasis, angiogenesis, and autophagy. We also present the most recent achievements in the development of new drugs targeting these isozymes. Finally, we discuss potential combination therapies using PFKFB3 inhibitors, which may represent important future cancer treatment options.

Curcumin is a turmeric, antioxidative compound, well-known of its anti-cancer properties. Nowadays more and more effort is made in the field of enhancing the efficiency of the anticancer therapies. Combining the photoactive properties of curcumin with the superficial localization of melanoma and photodynamic therapy (PDT) seems to be a promising treatment method. The research focused on the evaluation of the curcumin effectiveness as an anticancer therapeutic agent in the in vitro treatment of melanotic (A375) and amelanotic (C32) melanoma cell lines. Keratinocytes (HaCat) and fibroblasts (HGF) were used to assess the impact of the therapy on the skin tissue. The aim of the study was to investigate the cell death after exposure to light irradiation after preincubation with curcumin. Additionaly the authors analized the interactions between curcumin and the actin cytoskeleton. The cytotoxic effect initiated by curcumin and increased by irradiation confirm the usefulness of the flavonoid in the PDT approach. Depending on curcumin concentration and incubation time, melanoma cells survival rate ranged from: 93.68 % (C32 cell line, 10 μM, 24 h) and 83.47 % (A375 cell line, 10 μM, 24 h) to 8.98 % (C32 cell line, 50 μM, 48 h) and 12.42 % (A375 cell line, 50 μM, 48 h). Moreover, photodynamic therapy with curcumin increased the number of apoptotic and necrotic cells in comparison to incubation with curcumin without irradiation. The study demonstrated that PDT induced caspase-3 overexpression and DNA cleavage in the studied cell lines. The cells revealed decreased proliferation after the therapy due to the actin cytoskeleton rearrangement. Although effective, the therapy remains not selective towards melanoma cells.

Cancers are one of the leading causes of deaths affecting millions of people around the world, therefore they are currently a major public health problem. The treatment of cancer is based on surgical resection, radiotherapy, chemotherapy or immunotherapy, much of which is often insufficient and cause serious, burdensome and undesirable side effects. For many years, assorted secondary metabolites derived from plants have been used as antitumor agents. Recently, researchers have discovered a large number of new natural substances which can effectively interfere with cancer cells’ metabolism. The most famous groups of these compounds are topoisomerase and mitotic inhibitors. The aim of the latest research is to characterize natural compounds found in many common foods, especially by means of their abilities to regulate cell cycle, growth and differentiation, as well as epigenetic modulation. In this paper, we focus on a review of recent discoveries regarding nature-derived anticancer agents.

Background/Aim: The occurrence of BRAF^V600E mutation causes an up-regulation of the B-raf kinase activity leading to the stabilization of hypoxia-inducible factor 1-alpha (HIF-1α) - the promoter of the 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) enzyme. The aim of the study was to examine the effect of the (2E)-3-(3-Pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO), as an inhibitor of PFKFB3, on human melanoma cells (A375) with endogenous BRAF^V600E mutation. Materials and Methods: A375 cells were exposed to different concentrations of 3PO and the following tests were performed: docking, cytotoxicity assay, immunocytochemistry staining glucose uptake, clonogenic assay, holotomography imaging, and flow cytometry. Results: Our studies revealed that 3PO presents a dose-dependent and time-independent cytotoxic effect and promotes apoptosis of A375 cells. Furthermore, the obtained data indicate that 3PO induces cell cycle arrest in G1/0 and glucose uptake reduction. Conclusion: Taking all together, our research demonstrated a here should be proapoptotic and antiproliferative effect of 3PO on A375 human melanoma cells.