Epidemiological studies have revealed that high consumption of soy products is associated with low incidences of hormone-dependent cancers, including breast and prostate cancer. Soybeans contain large amounts of isoflavones, such as the genistein and daidzain. Previously, it has been demonstrated that genistein, one of the predominant soy isoflavones, can inhibit several steps involved in carcinogenesis. It is suggested that genistein possesses pleiotropic molecular mechanisms of action including inhibition of tyrosine kinases, DNA topoisomerase II, 5α-reductase, galectin-induced G₂/M arrest, protein histidine kinase, and cyclin-dependent kinases, modulation of different signaling pathways associated with the growth of cancer cells (e.g., NF-κB, Akt, MAPK), etc. Moreover, genistein is also a potent inhibitor of angiogenesis. Uncontrolled angiogenesis is considered as a key step in cancer growth, invasion, and metastasis. Genistein was found to inhibit angiogenesis through regulation of multiple pathways, such as regulation of VEGF, MMPs, EGFR expressions and NF-κB, PI3-K/Akt, ERK1/2 signaling pathways, thereby causing strong antiangiogenic effects. This review focuses on the antiangiogenic properties of soy isoflavonoids and examines their possible underlying mechanisms.

Chalcones are precursors of flavonoid biosynthesis in plants. Both flavonoids and chalcones are intensively investigated because of a large spectrum of their biological activities. Among others, anticancer and antiangiogenic effects account for the research interest of these substances. Because of an essential role in cancer growth and metastasis, angiogenesis is considered to be a promising target for cancer treatment. Currently used antiangiogenic agents are either synthetic compounds or monoclonal antibodies. However, there are some limitations of their use including toxicity and high price, making the search for new antiangiogenic compounds very attractive. Nowadays it is well known that several natural compounds may modulate basic steps in angiogenesis. A lot of studies, also from our lab, showed that phytochemicals, including polyphenols, are potent modulators of angiogenesis. This review paper is focused on the antiangiogenic effect of flavonoids and chalcones and discusses possible underlying cellular and molecular mechanisms.

Reactive oxygen species (ROS) are highly considered in the ethiopathogenesis of different pathological conditions because they may cause significant damage to cells and tissues. In this paper, we focused on potential antioxidant properties of two medical plants such as the Agrimonia eupatoria L. and Cynara cardunculus L. Both plants have previously been studied for their pharmacological activities, especially as hepatoprotective and hypoglycemic activities. It has been suggested, that their effects are related to the antioxidant properties of polyphenols, which are dominant compounds of the plants’ extracts. In the present study HPLC-MS analysis of water infusion was performed allowing the identification of several phenolic constituents. Furthermore, antioxidant effects of the two extracts were compared showing higher effects for agrimony extract compared to artichoke. Thus, agrimony was selected for the in vivo study using the skin flap viability model. In conclusion, our results provide evidence that the A. eupatoria extract may be a valuable source of polyphenols to be studied for the future development of supplements useful in the prevention of diseases linked to oxidative stress.

In the present study we evaluated the anti-angiogenic activities of β-escin (the major active compound of Aesculus hippocastanum L. seeds). Human umbilical-vein endothelial cells (HUVECs) were used as an in vitro model for studying the molecular mechanism underlying the anti-angiogenic effect of β-escin. We investigated the in vitro effects on proliferation, migration, and tube formation of HUVECs and in vivo anti-angiogenic activity was evaluated in a chick chorioallantoic membrane (CAM) angiogenesis assay. Moreover, the effect on gene expressions was determined by the RT2 ProfilerTM human angiogenesis PCR Array. It was found that β-escin exerts inhibitory effect on the basic fibroblast growth factor (bFGF)-induced proliferation, migration and tube formation, as well as CAM angiogenesis in vivo. The inhibition of critical steps of angiogenic process observed with β-escin could be partially explained by suppression of Akt activation in response to bFGF. Moreover, the anti-angiogenic effects of β-escin could also be mediated via inhibition of EFNB2 and FGF-1 gene expressions in endothelial cells. In conclusion, β-escin affects endothelial cells as a negative mediator of angiogenesis in vitro and in vivo and may therefore be considered as a promising candidate for further research elucidating its underlying mechanism of action.

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal malignancies and remains highly resistant to systemic chemotherapy. Tigecycline, a glycylcycline antibiotic that inhibits mitochondrial translation, has recently attracted attention as a potential candidate for drug repurposing in oncology because of its proposed chemosensitizing effects. The aim of this study was to evaluate the cytotoxic and chemosensitizing effects of tigecycline in combination with clinically relevant PDAC chemotherapy regimens, namely FOLFIRINOX (folinic acid, 5-fluorouracil, irinotecan, and oxaliplatin) and Gem-Pac (gemcitabine plus nab-paclitaxel). The individual components of these regimens were applied at clinically relevant molar ratios reflecting patient treatment protocols. Experiments were performed using both 2D monolayer cultures and 3D spheroid models of four PDAC cell lines (PaTu-8902, PANC-1, MIAPaCa-2, and Capan-2). Cell viability and proliferation were assessed using MTS assay, BrdU incorporation, and CellTiter-Glo ^® 3D assays, and spheroid growth dynamics were quantified by imaging-based area measurements after 3 days of treatment. Tigecycline enhanced the cytotoxic effects of both chemotherapy regimens in a concentration- and cell line-dependent manner, with a more pronounced effect observed in combination with Gem-Pac. In MTS assays, tigecycline converted otherwise chemoresistant cell lines (PaTu-8902, PANC-1, and MIAPaCa-2) into more responsive phenotypes, with the strongest sensitization observed in PaTu-8902 cells. Δ effect analysis further revealed that tigecycline-mediated sensitization to Gem-Pac occurred across a broad concentration range. Notably, this effect was evident even at lower, otherwise ineffective doses in Capan-2 cells. In contrast, the effect of tigecycline in combination with FOLFIRINOX was rather moderate and predominantly observed at higher concentrations. These trends were consistent with BrdU and 3D spheroid models, which supported the observed cell line-dependent differences in treatment response. Clinically relevant, tigecycline alone exhibited concentration-dependent cytotoxicity, with minimal effects at lower concentrations and more pronounced reductions in viability at higher doses. Overall, these findings demonstrate that tigecycline can enhance the efficacy of clinically relevant PDAC chemotherapy regimens in vitro and support its further preclinical evaluation as a potential adjunct to existing PDAC treatment strategies.