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Reactive oxygen species (ROS) serve as critical signals in various cellular processes. Excessive ROS cause cell death or senescence and mediates the therapeutic effect of many cancer drugs. Recent studies showed that ROS increasingly accumulate during G2/M arrest, the underlying mechanism, however, has not been fully elucidated. Here, we show that in cancer cells treated with anticancer agent TH287 or paclitaxel that causes M arrest, mitochondria accumulate robustly and produce excessive mitochondrial superoxide, which causes oxidative DNA damage and undermines cell survival and proliferation. While mitochondrial mass is greatly increased in cells arrested at M phase, the mitochondrial function is compromised, as reflected by reduced mitochondrial membrane potential, increased SUMOylation and acetylation of mitochondrial proteins, as well as an increased metabolic reliance on glycolysis. CHK1 functional disruption decelerates cell cycle, spares the M arrest and attenuates mitochondrial oxidative stress. Induction of mitophagy and blockade of mitochondrial biogenesis, measures that reduce mitochondrial accumulation, also decelerate cell cycle and abrogate M arrest-coupled mitochondrial oxidative stress. These results suggest that cell cycle progression and mitochondrial homeostasis are interdependent and coordinated, and that impairment of mitochondrial homeostasis and the associated redox signaling may mediate the antineoplastic effect of the M arrest-inducing chemotherapeutics. Our findings provide insights into the fate of cells arrested at M phase and have implications in cancer therapy., (© 2021. The Author(s).)

Fluorene-9-bisphenol (9,9-bis(4-hydroxyphenyl)-fluorene [BHPF]) is a bisphenol A (BPA) substitute used in the production of "BPA-free" plastics, now has been identified is harmful to living organisms. Our previous study showed that BHPF impaired mouse denuded oocyte in vitro maturation. However, there is a question that whether BHPF is still able to affect oocyte maturation in the presence of dense cumulus cells. In the present study, we checked the toxic effects of BHPF on porcine oocyte maturation which is derived from COCs in vitro culture. Our results showed that BHPF (50 μM) inhibited the expansion of cumulus cells, led to a significant decrease in polar body extrusion (PBE). Importantly, BHPF resulted in abnormal spindle assembly, ATP level decrease, reactive oxygen species (ROS) accumulation and early apoptosis in porcine oocytes, which are all negative to oocyte maturation. Furthermore, BHPF also declined porcine oocyte quality by disturbing the cortical granules (CGs) distribution. In conclusion, our study showed that BHPF still inhibited oocyte maturation even in the presence of cumulus cells leading to abnormal spindle assembly, ATP decrease, increased ROS level, early apoptosis, and disturbed CGs distribution in porcine oocytes, and also indicates that BHPF has a wide range toxic effects on oocyte in different species., (© 2019 Wiley Periodicals, Inc.)

Isoliensinine, liensinine and neferine are major bisbenzylisoquinoline alkaloids in the seed embryo of lotus (Nelumbo nucifera), and exhibit potential anti-cancer activity. Here, we explored the effects of these alkaloids on triple-negative breast cancer cells and found that among the three alkaloids isoliensinine possesses the most potent cytotoxic effect, primarily by inducing apoptosis. Interestingly, isoliensinine showed a much lower cytotoxicity against MCF-10A, a normal human breast epithelial cell line. Further studies showed that isoliensinine could significantly increase the production of reactive oxygen species (ROS) in triple-negative breast cancer cells, but not in MCF-10A cells. The isoliensinine-induced apoptosis could be attenuated by radical oxygen scavenger N-acetyl cysteine, suggesting that the cytotoxic effect of isoliensinine on cancer cells is at least partially achieved by inducing oxidative stress. We found that both p38 MAPK and JNK signaling pathways were activated by isoliensinine treatment and contributed to the induction of apoptosis. Furthermore, inhibitors or specific siRNAs of p38 MAPK and JNK could attenuate apoptosis induced by isoliensinine. However, only the p38 inhibitor or p38-specific siRNA blocked the elevation of ROS in isoliensinine-treated cells. Our findings thus revealed a novel antitumor effect of isoliensinine on breast cancer cells and may have therapeutic implications.

Tumor suppressor p53 is known to regulate the level of intracellular reactive oxygen species (ROS). It can either alleviate oxidative stress under physiological and mildly stressed conditions or exacerbate oxidative stress under highly stressed conditions. We here report that a p53-ROS positive feedback loop drives a senescence program in normal human fibroblasts (NHFs) and this senescence-driving loop is negatively regulated by CUL4B. CUL4B, which can assemble various ubiquitin E3 ligases, was found to be downregulated in stress-induced senescent cells, but not in replicative senescent cells. We observed that p53-dependent ROS production was significantly augmented and stress-induced senescence was greatly enhanced when CUL4B was absent or depleted. Ectopic expression of CUL4B, on the other hand, blunted p53 activation, reduced ROS production, and attenuated cellular senescence in cells treated with H2O2. CUL4B was shown to promote p53 ubiquitination and proteosomal degradation in NHFs exposed to oxidative stress, thus dampening the p53-dependent cellular senescence. Together, our results established a critical role of CUL4B in negatively regulating the p53-ROS positive feedback loop that drives cellular senescence., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The detection of Singlet oxygen (1O2) is of great interest to develop cancer therapies, because it can initiate a plethora of events that result in cell death. Singlet oxygen sensor green (SOSG) is considered the preferred probe because of its claimed high selectivity to Singlet oxygen (1O2). Although many researchers have used SOSG to detect 1O2 generation in Sonodynamic therapy (SDT) processes, the effect of ultrasound irradiation on SOSG has not been comprehensively evaluated. In this study, we conducted systematic experiments to determine SOSG activation in the presence of ultrasound irradiation. We found that the SOSG exhibited the abnormal physicochemical phenomena in distilled water in the presence of ultrasound. The fluorescence intensity of SOSG increased significantly when exposed to ultrasound alone. The results showed that there was a linear positive correlation between the treatment duration of different ultrasound intensities or SOSG concentrations and the fluorescence intensity of SOSG, respectively. In addition, scavenger tests also indicated that hydroxyl radicals (•OH) might be involved in the activation of SOSG. In conclusion, our results suggest that the influences of experimental conditions to SOSG must be fully considered, and that SOSG may not be a suitable probe for 1O2 in SDT. [ABSTRACT FROM AUTHOR]

The present study focused on examining the thermal population and non-radiative relaxation process by leveraging the unique characteristics of the triplet states of Platinum (Ⅱ) octaethylporphyrin (PtOEP). The investigation of the thermal population process involved the utilization of the luminescence exhibited by the PtOEP triplet state in an oxygen-free environment. Time-resolved spectroscopy was employed to investigate the non-radiative relaxation process occurring on the higher energy levels of the triplet states in the presence of oxygen. The findings indicate that both thermal population and non-radiative relaxation process follow the Boltzmann distribution law. Furthermore, the energy differences obtained from the fitting procedure closely aligned with the energy differences calculated based on the emission spectrum. This observation implies that the underlying reason for the congruence between these two processes is their inherent reversibility. [Display omitted] • Temperature-dependent thermal population and non-radiative relaxation processes were studied by utilizing Platinum (Ⅱ) octaethylporphyrin. • The thermal population process was conducted by examining the temperature-dependent luminescence spectra of PtOEP in an oxygen-free environment. • The non-radiative relaxation process was analyzed by time-resolved spectroscopy spectra in the presence of aerobic conditions. • The thermal population and non-radiative relaxation processes could be regarded as reversible process. [ABSTRACT FROM AUTHOR]

• The effect of imidazole on the Φ Δ of DVDMS was analyzed. • Φ Δ decreased from 0.91 to 0.33 as imidazole added into the DVDMS solution. • The optical properties of DVDMS under different imidazole dosage were measured to study the reason for the decrease of Φ Δ. • The reason for the reduction of Φ Δ was revealed based on the photophysicochemical process of 1O 2 generation. In this paper, the effect of imidazole on the singlet oxygen quantum yield (Φ Δ) of sinoporphyrin sodium (DVDMS) was studied. A relative method was used to measure Φ Δ with Rose Bengal (RB) as the reference and 1,3-diphenylisobenzofuran (DPBF) as the singlet oxygen trapping reagent. It can be found that Φ Δ of DVDMS decreased with the increment of imidazole concentration, and kept 0.33 after the imidazole concentration was above 0.26 M. The process of 1O 2 generation and optical properties of DVDMS in different imidazole concentrations were studied to analyze the reason for the above behavior. The invariability of UV–vis absorption and photoluminescence spectra suggested that the reduction of Φ Δ was attributed to the decrease of interaction between DVDMS and O 2 , which was caused by the surrounding of imidazole on DVDMS. For efficient implementation of PDT, it is necessary to identify the factors that may reduce the effect of PDT. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) are known to cause many types of DNA lesions that could be converted into cancer-promoting genetic alterations. Evidence showed that tumor suppressor p53 plays an important role in regulating the generation of cellular ROS, either by reducing oxidative stress under physiological and mildly stressed conditions, or by promoting oxidative stress under highly stressed conditions. In this report we characterized the effect of oxidative stress on the induction of micronuclei, especially the subclass marked by pan-staining of γ-H2AX or MN-γ-H2AX (+). We found that MN-γ-H2AX (+) were more responsive to hydrogen peroxide (H 2 O 2 ) than the MN-γ-H2AX (−). In human and mouse cells that are deficient in p53, the frequency of MN-γ-H2AX (+) is significantly elevated, but can be attenuated by antioxidant N-acetylcysteine (NAC). Depletion of p53-regulated antioxidant gene SESN1 by RNA interference also resulted in an elevation of MN-γ-H2AX (+). Furthermore, we found that in cells that were depleted of p400 by RNAi, and therefore were experiencing increased ROS, the frequency of MN-γ-H2AX (+), but not that of MN-γ-H2AX (−), was significantly induced. We further demonstrated that the induction of MN-γ-H2AX (+) by replication stress can also be attenuated by NAC, and that H 2 O 2 also leads to increased phosphorylation of Chk1 and Rad17 that mimics replication stress, suggesting that replication stress and oxidative stress are intertwined and may reinforce each other in driving genomic instability. Our findings illustrate the importance of p53-regulated redox level in the maintenance of genomic stability. [ABSTRACT FROM AUTHOR]