Drug-induced senescence program may be activated both in normal and cancer cells as a consequence of chemotherapeutic treatment, leading to some adverse side effects such as senescence-associated secretory phenotype (SASP), secondary senescence, and cancer promotion. Targeted elimination of senescent cells can be achieved by drugs with senolytic activity (senolytics), for example, the plant-derived natural compound quercetin, especially when co-treated with kinase inhibitor dasatinib. In the present study, three quercetin derivatives were synthesized and tested for improved senolytic action against etoposide-induced senescent human normal mammary epithelial cells and triple-negative breast cancer cells in vitro. Transformation of catechol moiety into diphenylmethylene ketal and addition of three acetyl groups to the quercetin molecule (QD3 derivative) promoted the clearance of senescent cancer cells as judged by increased apoptosis compared to etoposide-treated cells. A QD3-mediated senolytic effect was accompanied by decreased SA-beta galactosidase activity and the levels of p27, IL-1β, IL-8, and HSP70 in cancer cells. Similar effects were not observed in senescent normal cells. In conclusion, a novel senolytic agent QD3 was described as acting against etoposide-induced senescent breast cancer cells in vitro. Thus, a new one-two punch anti-cancer strategy based on combined action of a pro-senescence anti-cancer drug and a senolytic agent is proposed.

Mitochondria, the main cellular power stations, are important modulators of redox-sensitive signaling pathways that may determine cell survival and cell death decisions. As mitochondrial function is essential for tumorigenesis and cancer progression, mitochondrial targeting has been proposed as an attractive anticancer strategy. In the present study, three mitochondria-targeted quercetin derivatives (mitQ3, 5, and 7) were synthesized and tested against six breast cancer cell lines with different mutation and receptor status, namely ER-positive MCF-7, HER2-positive SK-BR-3, and four triple-negative (TNBC) cells, i.e., MDA-MB-231, MDA-MB-468, BT-20, and Hs 578T cells. In general, the mito-quercetin response was modulated by the mutation status. In contrast to unmodified quercetin, 1 µM mitQ7 induced apoptosis in breast cancer cells. In MCF-7 cells, mitQ7-mediated apoptosis was potentiated under glucose-depleted conditions and was accompanied by elevated mitochondrial superoxide production, while AMPK activation-based energetic stress was associated with the alkalization of intracellular milieu and increased levels of NSUN4. Mito-quercetin also eliminated doxorubicin-induced senescent breast cancer cells, which was accompanied by the depolarization of mitochondrial transmembrane potential. Limited glucose availability also sensitized doxorubicin-induced senescent breast cancer cells to apoptosis. In conclusion, we show an increased cytotoxicity of mitochondria-targeted quercetin derivatives compared to unmodified quercetin against breast cancer cells with different mutation status that can be potentiated by modulating glucose availability.

Pregnancy and childbirth are associated with the forming of reactive oxygen species that generate oxidative stress. Oxidative stress is a factor that may adversely affect the development of the fetus and the course of labour. Monitoring the parameters of oxidative stress can be used to assess the risk of health issues in the course of pregnancy and the condition of the newborn. Therefore, the analysis of oxidative stress in the physiological course of labour is the basis for understanding the role of oxidative stress in the pathogenesis of miscarriages and neonatal health circumstances. The study aimed to assess oxidative stress of mother-child pairs in the venous blood and umbilical cord blood at the time of physiological labour. One hundred and sixty-eight mother-child pairs were recruited to donate the mother’s venous blood in the first stage of labour and the venous umbilical cord blood after the newborn’s birth. Total antioxidant status (TAS), the activity of superoxide dismutase (SOD) with cofactors (Zn, Cu, Mn) and the activity of glutathione peroxidase (GPx) were analysed in venous blood plasma and umbilical cord blood. TAS value (p = 0.034), GPx activity (p < 0.001) and Zn concentration (p = 0.007) were significantly lower in maternal blood plasma as compared to neonatal umbilical cord blood. However, the activity of SOD (p = 0.013) and the concentration of Cu (p < 0.001) were significantly higher in the blood of mothers than of new-borns. The concentration of Mn in the plasma of the mother’s blood and the umbilical cord blood of the newborns was similar. Our research indicates higher levels of antioxidant enzyme (GPx) and total antioxidant potential (TAS) in umbilical cord blood compared to maternal blood, which may suggest depletion of redox reserves in women’s blood during labour.

Background/Objectives: Oxidative stress is a factor that may adversely affect the development of the foetus, the course of labour, and newborn health. This study aimed to determine the association between the labour method, oxidative stress parameters, and neonatal condition. Methods: The study material was umbilical cord blood from newborns delivered vaginally (n = 60) or by caesarean section (n = 108). The total antioxidant status (TAS), superoxide dismutase activity (SOD), glutathione peroxidase activity (GPx), and glutathione reductase activity (GR) were determined using colorimetric methods. The concentration of the chemical elements (Zn, Cu, Mn) was estimated, using atomic absorption spectrometry (ASA). Results: The SOD activity was significantly lower in newborns with an Apgar score below 10 at the 5th minute of life compared to newborns with the highest Apgar points (p = 0.041). In neonates delivered by caesarean section (CS), but not vaginally born (VB) neonates, the SOD activity was significantly lower in newborns with Apgar scores less than 10 at the 5th minute of life compared to newborns with the maximum number of Apgar points (p = 0.02). Conclusions: The reduced SOD activity in the umbilical cord blood of newborns with Apgar scores less than 10 could be related to increased oxidative stress during labour. Bupivacaine-induced oxidative stress seems to be the cause of SOD downregulation in caesarean-delivered newborns. The observed SOD downregulation in neonates delivered by CS and with a decreased Apgar score requires confirmation based on a larger cohort of neonates.