Angiogenesis is the process through which new blood vessels are formed from pre-existing ones. Exosomes are involved in angiogenesis in cancer progression by transporting numerous pro-angiogenic biomolecules like vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMPs), and microRNAs. Exosomes promote angiogenesis by suppressing expression of factor-inhibiting hypoxia-inducible factor 1 (HIF-1). Uptake of tumor-derived exosomes (TEX) by normal endothelial cells activates angiogenic signaling pathways in endothelial cells and stimulates new vessel formation. TEX-driven cross-talk of mesenchymal stem cells (MSCs) with immune cells blocks their anti-tumor activity. Effective inhibition of tumor angiogenesis may arrest tumor progression. Bevacizumab, a VEGF-specific antibody, was the first antiangiogenic agent to enter the clinic. The most important clinical problem associated with cancer therapy using VEGF- or VEFGR-targeting agents is drug resistance. Combined strategies based on angiogenesis inhibitors and immunotherapy effectively enhances therapies in various cancers, but effective treatment requires further research.

Currently, over 100 countries are fighting against a common enemy, the severe acute respiratory syndrome coronavirus (SARS‐CoV)‐2, which causes COVID‐19. This has created a demand for a substance whose effectiveness has already been demonstrated in a similar scenario. Glycyrrhizin (GZ) is a promising agent against SARS‐CoV‐2 as its antiviral activity against SARS‐CoV has already been confirmed. It is worthwhile to extrapolate from its proven therapeutic effects as there is a high similarity in the structure and genome of SARS‐CoV and SARS‐CoV‐2. There are many possible mechanisms through which GZ acts against viruses: increasing nitrous oxide production in macrophages, affecting transcription factors and cellular signalling pathways, directly altering the viral lipid‐bilayer membrane, and binding to the ACE2 receptor. In this review, we discuss the possible use of GZ in the COVID‐19 setting, where topical administration appears to be promising, with the nasal and oral cavity notably being the potent location in terms of viral load. The most recently published papers on the distribution of ACE2 in the human body and documented binding of GZ to this receptor, as well as its antiviral activity, suggest that GZ can be used as a therapeutic for COVID‐19 and as a preventive agent against SARS‐CoV‐2.

Ciprofloxacin (CP) has a confirmed cytotoxic action on some cancerous cells, but in high, non-pharmacological concentrations. Considering features of natural fatty acids, such as biocompatibility, biodegradability and their increased cellular uptake by cancer cells, it seems that combining them with a drug could improve its bioavailability, and thus cytotoxicity. Therefore, the aim of this study was coupling of CP with saturated and unsaturated fatty acids, and evaluation of their cytotoxicity, apoptosis-inducing effects and inhibition of IL-6 release in human primary (SW480) and metastatic (SW620) colon cancer, metastatic prostate cancer (PC3) and normal (HaCaT) cell lines. The PC3 cell line was the most sensitive to the presence of the obtained conjugates. The value of IC50 for oleic acid conjugate (4) was 7.7 μM, and it was 12 times lower than for CP alone (101.4 μM). The studied derivatives induced late apoptosis in all cancer cell lines, but not in normal cells. The most potent apoptosis inducer was conjugate 4, that resulted in the highest percentage of PC3 cells in late apoptosis (81.5% ± 3.9), followed by elaidic acid amide 5 (75% ± 4.8). The strongest pro-apoptic effects on SW480 cells were demonstrated by conjugates of DHA (8) and sorbic (2) acids, whereas in SW620 cell lines, compounds 2 and 5 appeared to be the most effective. To establish the mechanism of cytotoxic action of derivatives 2, 4, 5, the level of interleukin-6 (IL-6) was measured. The compounds with the highest cytotoxic potential significantly decreased the release of IL-6 by cancer cells. Additionally, all conjugates were evaluated for their in vitro antimicrobial activity. Short chain amides - crotonic (1) and sorbic (2) - were the most active against Staphyloccoci. The second-mentioned amide has shown both strong antistaphylococcal and antitumor properties.

Enoxacin as a second-generation synthetic quinolone is known for its antibacterial action; however, in recent years there have been studies focusing on its anticancer potential. Interestingly, it turns out that compared to other fluoroquinolones, enoxacin exhibits uncommon cytotoxic properties. Besides its influence on apoptosis, the cell cycle and cell growth, it exhibits a regulatory action on microRNA biogenesis. It was revealed that the molecular targets of the enoxacin-mediated inhibition of osteoclastogenesis are vacuolar H⁺-ATPase subunits and the c-Jun N-terminal kinase signaling pathway, causing a decrease in cell invasiveness. Interestingly, the prooxidative nature of the subjected fluoroquinolone enhanced the cytotoxic effect. Crucial for the anticancer activity were the carboxyl group at the third carbon atom, fluorine at the seventh carbon atom and nitrogen at the eighth position of naphyridine. Modifications of the parent drug improved the induction of oxidative stress, cell cycle arrest and the dysregulation of microRNA. The inhibition of V-ATPase–microfilament binding was also observed. Enoxacin strongly affected various cancer but not normal cells, excluding keratinocytes, which suffered from phototoxicity. It seems to be an underestimated anticancer drug with pleiotropic action. Furthermore, its usage as a safe antibiotic with well-known pharmacokinetics and selectivity will enhance the development of anticancer treatment strategies. This review covers articles published within the years 2000–2021, with a strong focus on the recent years (2016–2021). However, some canonical papers published in twentieth century are also mentioned.