Calixarene-mediated assembly of water-soluble C60-attached ultrathin graphite hybrids for efficient activation of reactive oxygen species to treat neuroblastoma cells

2020 ◽  
Vol 56 (53) ◽  
pp. 7325-7328 ◽  
Author(s):  
Jingxin Mo ◽  
Meiying Li ◽  
Xianjue Chen ◽  
Qinghua Li

Water-soluble hybrid of C60 on ultrathin graphite enables efficient activation of reactive oxygen species for enhanced phototoxicity to neuroblastoma cells.

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Amnah M. Alshangiti ◽  
Eszter Tuboly ◽  
Shane V. Hegarty ◽  
Cathal M. McCarthy ◽  
Aideen M. Sullivan ◽  
...  

Neuroblastoma is an embryonal malignancy that arises from cells of sympathoadrenal lineage during the development of the nervous system. It is the most common pediatric extracranial solid tumor and is responsible for 15% of childhood deaths from cancer. Fifty percent of cases are diagnosed as high-risk metastatic disease with a low overall 5-year survival rate. More than half of patients experience disease recurrence that can be refractory to treatment. Amplification of the MYCN gene is an important prognostic indicator that is associated with rapid disease progression and a poor prognosis, highlighting the need for new therapeutic approaches. In recent years, there has been an increasing focus on identifying anticancer properties of naturally occurring chalcones, which are secondary metabolites with variable phenolic structures. Here, we report that 4-hydroxychalcone is a potent cytotoxin for MYCN-amplified IMR-32 and SK-N-BE (2) neuroblastoma cells, when compared to non-MYCN-amplified SH-SY5Y neuroblastoma cells and to the non-neuroblastoma human embryonic kidney cell line, HEK293t. Moreover, 4-hydroxychalcone treatment significantly decreased cellular levels of the antioxidant glutathione and increased cellular reactive oxygen species. In addition, 4-hydroxychalcone treatment led to impairments in mitochondrial respiratory function, compared to controls. In support of this, the cytotoxic effect of 4-hydroxychalcone was prevented by co-treatment with either the antioxidant N-acetyl-L-cysteine, a pharmacological inhibitor of oxidative stress-induced cell death (IM-54) or the mitochondrial reactive oxygen species scavenger, Mito-TEMPO. When combined with the anticancer drugs cisplatin or doxorubicin, 4-hydroxychalcone led to greater reductions in cell viability than was induced by either anti-cancer agent alone. In summary, this study identifies a cytotoxic effect of 4-hydroxychalcone in MYCN-amplified human neuroblastoma cells, which rationalizes its further study in the development of new therapies for pediatric neuroblastoma.


2004 ◽  
Vol 112 (2) ◽  
pp. 219-224 ◽  
Author(s):  
Shinya Osone ◽  
Hajime Hosoi ◽  
Yasumichi Kuwahara ◽  
Yoshifumi Matsumoto ◽  
Tomoko Iehara ◽  
...  

Author(s):  
Ekaterina Kovel ◽  
Anna Sachkova ◽  
Natalia Vnukova ◽  
Grigoriy Churilov ◽  
Elena Knyazeva ◽  
...  

Fullerenols are nanosized water-soluble polyhydroxylated derivatives of fullerenes, specific allotropic form of carbon, bioactive compounds and perspective pharmaceutical agents. We studied biological effects of a series of fullerenols. Antioxidant activity and toxicity of the fullerenols were compared using bioluminescence assays (cellular and enzymatic); a content of Reactive Oxygen Species in fullerenol solutions was determined using chemiluminescence luminol method. Two groups of fullerenols with different number of hydroxyl substituents were under investigation: (I) С60Оy(OH)x, С60,70Оy(OH)x, where х+у=24–28 and (II) С60,70Оy(OH)x, Fe0,5С60Оy(OH)x, where х+у=40–42. Toxicity of the fullerenols was evaluated using effective concentrations ЕС50. Fullerenol’ antioxidant activity was investigated in model solutions of organic toxicant of oxidative type, 1,4-benzoquinone. Detoxification coefficients were calculated to analyze and compare the antioxidant activity. Higher toxicity and lower antioxidant activity were demonstrated in the solutions of fullerenols with higher number of the oxygen substituents (х+у=40–42). The differences were concerned with fullerenol’ ability to disturb Reactive Oxygen Species balance in aqueous solutions. Toxic effect of the prospective endohedral metal-fullerenol with gadolinium atom involved, Gd@C82Oy(OH)x, where х+у=40–42, was evaluated and explained by a high number of oxygen groups


2010 ◽  
Vol 128 (10) ◽  
pp. 2481-2494 ◽  
Author(s):  
Rajasubramaniam Shanmugam ◽  
Praveen Kusumanchi ◽  
Hitesh Appaiah ◽  
Liang Cheng ◽  
Peter Crooks ◽  
...  

2014 ◽  
Vol 14 (23) ◽  
pp. 12915-12930 ◽  
Author(s):  
V. Verma ◽  
T. Fang ◽  
H. Guo ◽  
L. King ◽  
J. T. Bates ◽  
...  

Abstract. We assess the potential of the water-soluble fraction of atmospheric fine aerosols in the southeastern United States to generate reactive oxygen species (ROS) and identify major ROS-associated emission sources. ROS-generation potential of particles was quantified by the dithiothreitol (DTT) assay and involved analysis of fine particulate matter (PM) extracted from high-volume quartz filters (23 h integrated samples) collected at various sites in different environmental settings in the southeast, including three urban-Atlanta sites, in addition to a rural site. Paired sampling was conducted with one fixed site in Atlanta (Jefferson Street), representative of the urban environment, with the others rotating among different sites, for ~250 days between June 2012 and September 2013 (N=483). A simple linear regression between the DTT activity and aerosol chemical components revealed strong associations between PM ROS-generation potential and secondary organic aerosol (WSOC – water-soluble organic carbon) in summer, and biomass burning markers in winter. Redox-active metals were also somewhat correlated with the DTT activity, but mostly at urban and roadside sites. Positive matrix factorization (PMF) was applied to apportion the relative contribution of various sources to the ROS-generation potential of water-soluble PM2.5 in urban Atlanta. PMF showed that vehicular emissions contribute uniformly throughout the year (12–25%), while secondary oxidation processes dominated the DTT activity in summer (46%) and biomass burning in winter (47%). Road dust was significant only during drier periods (~12% in summer and fall). Source apportionment by chemical mass balance (CMB) was reasonably consistent with PMF, but with higher contribution from vehicular emissions (32%). Given the spatially large data set of PM sampled over an extended period, the study reconciles the results from previous work that showed only region- or season-specific aerosol components or sources contributing to PM ROS activity, possibly due to smaller sample sizes. The ubiquitous nature of the major sources of PM-associated ROS suggests widespread population exposures to aerosol components that have the ability to catalyze the production of oxidants in vivo.


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