scholarly journals The anti-cancer agent guttiferone-A permeabilizes mitochondrial membrane: Ensuing energetic and oxidative stress implications

2011 ◽  
Vol 253 (3) ◽  
pp. 282-289 ◽  
Author(s):  
Gilberto L. Pardo-Andreu ◽  
Yanier Nuñez-Figueredo ◽  
Valeria G. Tudella ◽  
Osmany Cuesta-Rubio ◽  
Fernando P. Rodrigues ◽  
...  
2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Dongjie Peng ◽  
Junyan Li ◽  
Yue Deng ◽  
Xiaojuan Zhu ◽  
Lin Zhao ◽  
...  

Abstract Background The activation of NOD-like receptor protein 3 (NLRP3) inflammasome-dependent pyroptosis has been shown to play a vital role in the pathology of manganese (Mn)-induced neurotoxicity. Sodium para-aminosalicylic acid (PAS-Na) has a positive effect on the treatment of manganism. However, the mechanism is still unclear. We hypothesized that PAS-Na might act through NLRP3. Methods The microglial cell line BV2 and male Sprague-Dawley rats were used to investigate the impacts of PAS-Na on Mn-induced NLRP3 inflammasome-dependent pyroptosis. The related protein of the NF-κB pathway and NLRP3-inflammasome-dependent pyroptosis was detected by western blot. The reactive oxygen species and mitochondrial membrane potential were detected by immunofluorescence staining and flow cytometry. The activation of microglia and the gasdermin D (GSDMD) were detected by immunofluorescence staining. Results Our results showed that Mn treatment induced oxidative stress and activated the NF-κB pathway by increasing the phosphorylation of p65 and IkB-α in BV2 cells and in the basal ganglia of rats. PAS-Na could alleviate Mn-induced oxidative stress damage by inhibiting ROS generation, increasing mitochondrial membrane potential and ATP levels, thereby reducing the phosphorylation of p65 and IkB-α. Besides, Mn treatment could activate the NLRP3 pathway and promote the secretion of IL-18 and IL-1β, mediating pyroptosis in BV2 cells and in the basal ganglia and hippocampus of rats. But an inhibitor of NF-κb (JSH-23) treatment could significantly reduce LDH release, the expression of NLRP3 and Cleaved CASP1 protein and IL-1β and IL-18 mRNA level in BV2 cells. Interestingly, the effect of PAS-Na treatment in Mn-treated BV2 cells is similar to those of JSH-23. Besides, immunofluorescence results showed that PAS-Na reduced the increase number of activated microglia, which stained positively for GSDMD. Conclusion PAS-Na antagonized Mn-induced NLRP3 inflammasome dependent pyroptosis through inhibiting NF-κB pathway activation and oxidative stress.


2014 ◽  
pp. S601-S612 ◽  
Author(s):  
V. K. M. KHANDELWAL ◽  
L. M. MITROFAN ◽  
J. M. T. HYTTINEN ◽  
K. R. CHAUDHARI ◽  
R. BUCCIONE ◽  
...  

Several pre-clinical and clinical studies have demonstrated zoledronic acid (Zol), which regulates the mevalonate pathway, has efficient anti-cancer effects. Zol can also induce autophagy. The aim of this study is to add new understanding to the mechanism of autophagy induction by Zol. LC3B-II, the marker for autophagy was increased by Zol treatment in breast cancer cells. Autophagosomes induced by Zol were visualized and quantified in both transient (pDendra2-hLC3) and stable MCF-7-GFP-LC3 cell lines. Acidic vesicular organelles were quantified using acridine orange. Zol induced a dose and time dependent autophagy. Treatment of Zol increased oxidative stress in MCF-7 cells, which was reversed by GGOH or anti-oxidants. On the other hand, treatment with GGOH or anti-oxidants resulted in decreased levels of LC3B-II. Further, the induced autophagy was irreversible, as the washout of Zol after 2 h or 24 h resulted in similar levels of autophagy, as induced by continuous treatment after 72 h. Thus, it can be summarized that Zol can induce a dose dependent but irreversible autophagy, by its effect on the mevalonate pathway and oxidative stress. This study adds to the understanding of the mechanism of action of Zol, and that it can induce autophagy at clinically relevant shorter exposure times in cancer cells.


2011 ◽  
Vol 138-139 ◽  
pp. 1179-1182
Author(s):  
Chang Jun Lin ◽  
Han Chang Huang ◽  
Wen Juan Liu ◽  
Zhao Feng Jiang

Mitochondrial dysfunction and oxidative stress are among the earliest events linked to Alzheimer Disease and might play a causative role in disease onset and progression. In this paper, a biomedical imaging and visualization model was set to investigate the mitochondrial dysfunction and oxidative stress in Aβ/Cu2+-treated cells, which contribute in a significant manner to bioenergetic failure and mitochondrial dysfunction, by measuring mitochondrial membrane potential, Ca2+, chromatin condensation and ROS. This evaluating method opens a window for analyzing the protective effect of a certain substance in improving mitochondrial function and preventing oxidative stress in AD development.


Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5628
Author(s):  
Guangxing Li ◽  
Kaiyue Ding ◽  
Yanling Qiao ◽  
Liu Zhang ◽  
Luping Zheng ◽  
...  

Cancer is the second leading cause of death globally. Millions of persons die due to cancer each year. In the last two decades, the anticancer effects of natural flavonoids have become a hot topic in many laboratories. Meanwhile, flavonoids, of which over 8000 molecules are known to date, are potential candidates for the discovery of anticancer drugs. The current review summarizes the major flavonoid classes of anticancer efficacy and discusses the potential anti-cancer mechanisms through inflammation and oxidative stress action, which were based on database and clinical studies within the past years. The results showed that flavonoids could regulate the inflammatory response and oxidative stress of tumor through some anti-inflammatory mechanisms such as NF-κB, so as to realize the anti-tumor effect.


2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Min Jin ◽  
Hui Yu ◽  
Xia Jin ◽  
Lailai Yan ◽  
Jingyu Wang ◽  
...  

Background and Objectives. Dracocephalum moldavica L. is an herbal medicine used to treat cardiovascular diseases in China. The purpose of this study was to assess the cardioprotective effect of D. moldavica L. extracts against H2O2-induced apoptosis and oxidative stress in H9c2 cells and to explore the mechanism behind this effect. Materials and Methods. The petroleum ether (petrol), dichloromethane (CH2Cl2), ethyl acetate (EtOAc), and n-butyl alcohol (n-BuOH) fractions were isolated from alcohol extracts of D. moldavica L. Total phenolic and flavonoid contents and in vitro antioxidant activities of different fractions were evaluated. H9c2 cells were then treated with D. moldavica L. extracts before challenging with H2O2. Cell viability was determined by colorimetric assay, and ELISA was used to measure the levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), and superoxide dismutase (SOD). Apoptosis levels and mitochondrial membrane potential were measured by flow cytometry. The expressions of cell apoptosis regulatory proteins caspase-3, Bax, and Bcl-2 were determined by western blotting. Results. Our results demonstrated that the EtOAc fraction from D. moldavica L. ethanol extract, which is rich in phenolic and flavonoid active constituents, had the strongest free radical scavenging activity. Additionally, this fraction increased H2O2-induced reduction in cell viability, SOD activity, and mitochondrial membrane potential. It also reduced H2O2-induced elevation in ROS production, contents of LDH and MDA, and H9c2 apoptosis. We further found that the EtOAc fraction increased Bcl-2 expression, while it decreased caspase-3 and Bax expressions induced by H2O2 in H9c2 cells. Conclusions. Our data revealed that the EtOAc fraction from D. moldavica L. ethanol extract ameliorates H2O2-induced cardiotoxicity via antiapoptotic and antioxidant mechanisms.


2010 ◽  
Vol 22 (5) ◽  
pp. 856 ◽  
Author(s):  
Álvaro E. Domínguez-Rebolledo ◽  
María R. Fernández-Santos ◽  
Alfonso Bisbal ◽  
José Luis Ros-Santaella ◽  
Manuel Ramón ◽  
...  

Antioxidants could improve sperm media, extending the viability of spermatozoa and protecting their DNA. The protective ability of lipoic acid, melatonin, Trolox and crocin was tested on red deer spermatozoa incubated at 37°C. Cryopreserved spermatozoa were thawed and incubated with 1 mM or 0.1 mM of each antioxidant, with or without oxidative stress (100 μM Fe2+). Motility (CASA), viability, mitochondrial membrane potential and acrosomal status were assessed. Lipoperoxidation (malondialdehyde production), intracellular reactive oxygen species (ROS) and DNA status (TUNEL) were checked at 4 h. Incubation alone increased ROS and decreased motility. Oxidative stress intensified these effects, increasing lipoperoxidation and DNA damage. Lipoic acid had little protective effect, whereas 1 mM melatonin showed limited protection. Trolox lowered ROS and lipoperoxidation both in oxidised and non-oxidised samples. In oxidised samples, Trolox prevented DNA and acrosomal damage, and ameliorated motility. Crocin at 1 mM showed similar results to Trolox, but noticeably stimulated motility and had no effect on lipoperoxidation. In a second experiment, a broader range of crocin and melatonin concentrations were tested, confirming the effects of crocin (positive effects noticeable at 0.5–0.75 mM), but showing an increase in lipoperoxidation at 2 mM. Melatonin was increasingly effective at 2.5 and 5 mM (ROS, lipoperoxidation and DNA status). Crocin seems a promising new antioxidant, but its particular effects on sperm physiology must be further studied, especially the consequences of motility stimulation and confirming its effect on lipoperoxidation. Melatonin might be useful at relatively high concentrations, compared to Trolox.


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