Bioactive extracts of Ziziphus mauritiana induces apoptosis in A549 human lung epithelial carcinoma cells through the generation of reactive oxygen species

2021 ◽  
Vol 17 ◽  
Author(s):  
Om Prakash ◽  
Shazia Usmani ◽  
Amresh Gupta ◽  
Asif Jafri ◽  
Mohammad Fahad Ullah ◽  
...  

Background: In recent years, novel metabolites isolated from botanical sources have attracted much attention for traditional and therapeutic significance. The ethnopharmacological studies suggest that Ziziphus mauritiana is a common remedy against several kinds of ailments. Objective: The current study has evaluated the MeOH extract of Ziziphus mauritiana leaves (ZME) through physicochemical, phytochemical, and chromatographic fingerprinting analysis, which displayed an array of biometabolites of pharmacological significance including flavonoids. Methods: The extract was further examined for anticancer activities which revealed promising anticancer properties against human lung epithelial carcinoma cells (A549) and induction of apoptosis impart by ROS. The oxidative stress was evaluated in terms of production and accumulation of cytosolic extent of ROS whereas anticancer perspective was determined by MTT assay, cell morphology analysis, followed by nuclear condensation for the examination of apoptosis induction. Results: Finding suggests that the MeOH extract of ZME markedly exhibited promising anticancer activity against the A549 lung epithelial carcinoma cell. The ZME was found to be most active in the MTT assay against A549 cells while it was less toxic to normal cells. The intracellular ROS generation was remarkably induced by ZME, which correlated with the ability of the flavonoid-rich fractions in the MeOH extract to inhibit cell growth and might induce apoptosis. Conclusion: The present study provides useful insight concerning the promising anticancer potential of ZME against A549 lung carcinomas. However, the clinical correlation will be required for its authorization and in the discovery of significant and least noxious novel agents against lung carcinomas.

Author(s):  
Yun Wu ◽  
Mei Wang ◽  
Shaojuan Luo ◽  
Yunfeng Gu ◽  
Dongyang Nie ◽  
...  

Although nanoparticles (NPs) have been used as simplified atmospheric particulate matter (PM) models, little experimental evidence is available to support such simulations. In this study, we comparatively assessed the toxic effects of PM and typical NPs (four carbonaceous NPs with different morphologies, metal NPs of Fe, Al, and Ti, as well as SiO2 NPs) on human lung epithelial A549 cells. The EC50 value of PM evaluated by cell viability assay was 148.7 μg/mL, closest to that of SiO2 NPs, between the values of carbonaceous NPs and metal NPs. All particles caused varying degrees of reactive oxygen species (ROS) generation and adenosine triphosphate (ATP) suppression. TiO2 NPs showed similar performance with PM in inducing ROS production (p < 0.05). Small variations between two carbonaceous NPs (graphene oxides and graphenes) and PM were also observed at 50 μg/mL. Similarly, there was no significant difference in ATP inhibition between carbonaceous NPs and PM, while markedly different effects were caused by SiO2 NP and TiO2 NP exposure. Our results indicated that carbonaceous NPs could be served as potential surrogates for urban PM. The identification of PM model may help us further explore the specific roles and mechanisms of various components in PM.


2013 ◽  
Vol 28 (6) ◽  
pp. 497-503 ◽  
Author(s):  
Ryoko Yumoto ◽  
Sayuri Suzuka ◽  
Saori Nishimoto ◽  
Junya Nagai ◽  
Mikihisa Takano

2001 ◽  
Vol 280 (1) ◽  
pp. L30-L38 ◽  
Author(s):  
Jun Araya ◽  
Muneharu Maruyama ◽  
Kazuhiko Sassa ◽  
Tadashi Fujita ◽  
Ryuji Hayashi ◽  
...  

Radiation pneumonitis is a major complication of radiation therapy. However, the detailed cellular mechanisms have not been clearly defined. Based on the recognition that basement membrane disruption occurs in acute lung injury and that matrix metalloproteinase (MMP)-2 can degrade type IV collagen, one of the major components of the basement membrane, we hypothesized that ionizing radiation would modulate MMP-2 production in human lung epithelial cells. To evaluate this, the modulation of MMP-2 with irradiation was investigated in normal human bronchial epithelial cells as well as in A549 cells. We measured the activity of MMP-2 in the conditioned medium with zymography and the MMP-2 mRNA level with RT-PCR. Both of these cells constitutively expressed 72-kDa gelatinolytic activity, corresponding to MMP-2, and exposure to radiation increased this activity. Consistent with the data of zymography, ionizing radiation increased the level of MMP-2 mRNA. This radiation-induced increase in MMP-2 expression was mediated via p53 because the p53 antisense oligonucleotide abolished the increase in MMP-2 activity as well as the accumulation of p53 after irradiation in A549 cells. These results indicate that MMP-2 expression by human lung epithelial cells is involved in radiation-induced lung injury.


2020 ◽  
Author(s):  
Aleksandr Ianevski ◽  
Rouan Yao ◽  
Svetlana Biza ◽  
Eva Zusinaite ◽  
Andres Männik ◽  
...  

AbstractCombination therapies have become a standard for the treatment for HIV and HCV infections. They are advantageous over monotherapies due to better efficacy and reduced toxicity, as well as the ability to prevent the development of resistant viral strains and to treat viral co-infections. Here, we identify several new synergistic combinations against emerging and re-emerging viral infections in vitro. We observed synergistic activity of nelfinavir with investigational drug EIDD-2801 and convalescent serum against SARS-CoV-2 infection in human lung epithelial Calu-3 cells. We also demonstrated synergistic activity of vemurafenib combination with emetine, homoharringtonine, gemcitabine, or obatoclax against echovirus 1 infection in human lung epithelial A549 cells. We also found that combinations of sofosbuvir with brequinar and niclosamide were synergistic against HCV infection in hepatocyte derived Huh-7.5 cells, whereas combinations of monensin with lamivudine and tenofovir were synergistic against HIV-1 infection in human cervical TZM-bl cells. Finally, we present an online resource that summarizes novel and known antiviral drug combinations and their developmental status. Overall, the development of combinational therapies could have a global impact improving the preparedness and protection of the general population from emerging and re-emerging viral threats.


2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Qing Jiang ◽  
Michelle Moreland ◽  
Bruce Ames ◽  
Beate Illek ◽  
Jim Wagner ◽  
...  

2019 ◽  
Vol 20 (16) ◽  
pp. 3975 ◽  
Author(s):  
Mingqi Wang ◽  
Xinyu Cao ◽  
Chang Luan ◽  
Zhengqiang Li

Lung tissues are frequently exposed to a hyperoxia environment, which leads to oxidative stress injuries. Hydrogen sulfide (H2S) is widely implicated in physiological and pathological processes and its antioxidant effect has attracted much attention. Therefore, in this study, we used hydrogen peroxide (H2O2) as an oxidative damage model to investigate the protective mechanism of H2S in lung injury. Cell death induced by H2O2 treatment could be significantly attenuated by the pre-treatment of H2S, resulting in a decrease in the Bax/Bcl-2 ratio and the inhibition of caspase-3 activity in human lung epithelial cell line A549 cells. Additionally, the results showed that H2S decreased reactive oxygen species (ROS), as well as neutralized the damaging effects of H2O2 in mitochondria energy-producing and cell metabolism. Pre-treatment of H2S also decreased H2O2-induced suppression of endogenous H2S production enzymes, cystathionine-beta-synthase (CBS), cystathionine-gamma-lyase (CSE), and 3-mercapto-pyruvate sulfurtransferase (MPST). Furthermore, the administration of H2S attenuated [Ca2+] overload and endoplasmic reticulum (ER) stress through the mitogen-activated protein kinase (MAPK) signaling pathway. Therefore, H2S might be a potential therapeutic agent for reducing ROS and ER stress-associated apoptosis against H2O2-induced lung injury.


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