Chalcones are a type of natural flavonoid compound that have been found to possess promising anticancer properties. Studies have shown that chalcones can inhibit the growth and proliferation of cancer cells, induce apoptosis, and suppress tumor angiogenesis. In addition to their potential therapeutic applications, chalcones have also been studied for their chemopreventive effects, which involve reducing the risk of cancer development in healthy individuals. Overall, the anticancer properties of chalcones make them a promising area of research for developing new cancer treatments and preventative strategies. This review aims to provide a thorough overview of the central studies reported in the literature concerning cancer prevention and the treatment of chalcones. Although chalcones target many different mechanisms, the STAT and NF-κB signaling pathways are the ones this review will focus on, highlighting the existing crosstalk between these two pathways and considering the potential therapeutic opportunities for chalcone combinations.

The chemical composition of Succisa pratensis is not well known. The existing data indicate a substantial content of flavonoids, which include luteolin and apigenin 7-glucosides. The aim of this study was to elaborate the isolation protocol of these flavonoids from flowers and leaves of S. pratensis, to carry out their characterization, as well as evaluate the effect of S. pratensis extracts on activation of transcription factor NF-κB and α-amylase activity. The extraction protocol applied in this study allowed isolation and characterization of flavonoid fraction of S. pratensis. Their identity was confirmed by NMR spectra analysis, UV spectroscopy and electrospray ionization-tandem MS evaluation. Treatment of pancreatic α-amylase with S. pratensis extract inhibited this enzyme’s activity to an extent comparable to that of isolated luteolin and apigenin 7-glucosides. Incubation of HepG2 cells for 24 h with S. pratensis extracts or isolated flavonoids resulted in moderate reduction in NF-κB transcription factor activation evaluated in terms of translocation of its active subunits from cytosol into nucleus and subsequently diminished expression of the COX-2 gene. Expression of NF-κB was also reduced. The most significantly diminished NF-κB activation and expression, as well as COX-2 expression, was found to result from treatment with isolated flavonoids and ethyl acetate extract of S. pratensis leaves. These results indicate that S. pratensis flavonoids may modulate the metabolic and signaling pathways whose deregulation is related to pathogenesis of liver cancer. Further studies are required to confirm these observations and assess the chemopreventive and/or therapeutic potential of the S. pratensis herb.

The study aimed to evaluate the possible modulation of Nrf2, NF-ĸB and STAT3 signaling pathways in the colorectal cancer (CRC) cells line DLD-1 and HCT116 by secondary metabolites of lichens. An attempt was made to indicate the most promising targets in these signaling pathways. Attention was also paid to the effects of the compounds tested on CRC cells using anakoinosis—that is, simultaneous analysis of several signaling pathways. The effects of the tested natural compounds on the activity of selected transcriptional factors related to CRC were analyzed by Western blot and RT-PCR assays. The highest activity against CRC cells was shown by physodic and salazinic acids from the studied secondary metabolites of lichens. As a result, an increase in the activation of transcription factor Nrf2 and the expression of its selected target genes was observed. Physodic and salazinic acids induced the opposite effect in relation to the NF-κB and STAT3 pathways. These results confirmed our earlier observations that lichen-derived compounds have the ability to modulate signaling pathway networks. While caperatic acid affected Wnt/β-catenin to the most extent, salazinic acid was the most potent modulator of Nrf2, NF-κB and STAT3 pathways. Physodic acid seemed to affect all the investigated pathways.

Our previous study showed that the new synthetic methoxy-stilbenes, 3,4,2′-trimethoxy-trans-stilbene (3MS), 3,4,2′,4′-tetramethoxy-trans-stilbene (4MS), and 3,4,2′,4′,6′-pentamethoxy-trans-stilbene (5MS), modulate the constitutive expression of enzymes and receptors involved in estrogen metabolism in breast immortalized epithelial MCF10 cells. In this study, we evaluated the effect of 3MS, 4MS, and 5MS in comparison to resveratrol activity in MCF7 estrogen-dependent and MDA-MB-231 estrogen-independent breast cancer cell lines. 3MS similarly to resveratrol reduced the expression of estrogen receptor α in MCF7 cells. However, in these cells, 5MS reduced the most CYP19, the gene encoding aromatase, at mRNA transcript level. In contrast, in the MDA-MB-231 cells, the most efficient inhibitor of CYP19 expression was 3MS, reducing the level of its protein by ~ 25%. This stilbene also inhibited the aromatase activity in a recombinant protein system with IC₅₀ value ~ 85 µM. Treatment with the methoxy-stilbenes reduced the level of estradiol in culture medium. The most significant reduction was exerted by 3MS. None of the tested stilbenes including resveratrol changed significantly the expression of AhR, although CYP1A1 protein level was slightly reduced in MDA-MB-231 cells, while CYP1B1 expression was increased in these cells as a result of treatment with 3MS, but only at the transcript level. Overall, these results show weak or moderate effect of the new methoxy-stilbenes on the expression of key proteins involved in estrogens metabolism in cancer breast cells. However, the reduced CYP19 expression and activity upon 3MS treatment in metastatic MDA-MB-231 cells require the further studies.

Vulvar squamous cell carcinoma (VSCC) is a rare malignancy with a relatively good prognosis. However, the prognosis remains poor for elderly patients and those with a significant depth of tumor invasion; thus, novel treatment modalities are needed. The aim of this study was to analyze the impact of cannabidiol (CBD) and its combination with NSAIDs, diclofenac (DIC) and ibuprofen (IBU) on VSCC cells. In this regard, the MTT test was applied for cytotoxicity analysis. Moreover, the influence of CBD, DIC and IBU, as well as their combinations, on apoptosis and cell cycle distribution were analyzed by flow cytometry. The mechanisms of action of the analyzed compounds, including their impact on NF-κB signaling, p53 and COX-2 expression were evaluated using Western blot. This study shows that CBD and its combinations with NSAIDs are cytotoxic to A431 cells, but they also reduce, in a dose-dependent manner, the viability of immortalized keratinocyte HaCaT cells, and human umbilical vein cell line, EA.hy926. Moreover, the compounds and their combinations induced apoptosis, diminished the NF-κB signaling activation and reduced COX-2 expression. We conclude that CBD and its combination with DIC or IBU are promising candidates for the adjuvant treatment of high-risk VSCC patients. However, their impact on non-cancerous cells requires careful evaluation.

Colorectal cancer is a malignant tumour of the digestive system, more common in the elderly than in younger individuals. The incidence rate in the United States and the European Union is increasing by an average of 4.2% to 4.6% annually. There is emerging evidence that deregulation of the signalling pathway and abnormal expression and activation of genes is the main reason for the development of colorectal cancer. Signal transducer and activator of transcription (STAT3) is a transcription factor of signal transduction and transcriptional activation of target genes which plays important roles in proliferation, differentiation, apoptosis and other physiological processes. It has been confirmed that abnormal activation of STAT3 is involved in the development of tumours, so the identification of STAT3 inhibitors is a promising strategy for cancer chemoprevention and treatment of colorectal cancer. In this review, the roles of STAT3 in the pathogenesis and treatment of colorectal cancer are discussed.