scholarly journals Paraoxonase-2 Silencing Enhances Sensitivity of A375 Melanoma Cells to Treatment with Cisplatin

Antioxidants ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1238
Author(s):  
Roberto Campagna ◽  
Tiziana Bacchetti ◽  
Eleonora Salvolini ◽  
Valentina Pozzi ◽  
Elisa Molinelli ◽  
...  

Melanoma represents the most aggressive skin cancer, being responsible for the majority of deaths related with these neoplasms. Despite chemotherapy represents a frontline approach for management of the advanced stages of the disease, it displayed poor response rates and short-term efficacy due to melanoma cell resistance. Therefore, the discovery of molecules that can be used for effective targeted therapy of melanoma is crucial. In this study, we evaluated the impact of paraoxonase-2 (PON2) silencing on proliferation, viability, and resistance to treatment of the A375 melanoma cell line with chemotherapeutic drugs dacarbazine (DTIC) and cisplatin (CDDP). Due to the enzymes ability to counteract oxidative stress, we also evaluated the effect of enzyme knockdown on reactive oxygen species (ROS) production in cells treated with CDDP. The data reported clearly demonstrated that PON2 knockdown led to a significant reduction of cell proliferation and viability, as well as to an enhancement of A375 sensitivity to CDDP treatment. Moreover, enzyme downregulation was associated with an increase of ROS production in CDDP-treated cells. Although further analyses will be necessary to understand how PON2 could influence melanoma cell metabolism and phenotype, our results seem to suggest that the enzyme may serve as an interesting molecular target for effective melanoma treatment.

2004 ◽  
Vol 122 (2) ◽  
pp. 369-380 ◽  
Author(s):  
Cédric Hesling ◽  
Michel D'Incan ◽  
Pierre Souteyrand ◽  
Jean-Claude Monboisse ◽  
Sylvie Pasco ◽  
...  

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2987 ◽  
Author(s):  
Adrien Chouchou ◽  
Cindy Patinote ◽  
Pierre Cuq ◽  
Pierre-Antoine Bonnet ◽  
Carine Deleuze-Masquéfa

Imiqualines (imidazoquinoxaline derivatives) are anticancer compounds with high cytotoxic activities on melanoma cell lines. The first generation of imiqualines, with two lead compounds (EAPB0203 and EAPB0503), shows remarkable in vitro (IC50 = 1 570 nM and IC50 = 200 nM, respectively, on the A375 melanoma cell line) and in vivo activity on melanoma xenografts. The second generation derivatives, EAPB02302 and EAPB02303, are more active, with IC50 = 60 nM and IC50 = 10 nM, respectively, on A375 melanoma cell line. The aim of this study was to optimize the bioavailability of imiqualine derivatives, without losing their intrinsic activity. For that, we achieved chemical modulation on the second generation of imiqualines by conjugating amino acids on position 4. A new series of twenty-five compounds was efficiently synthesized by using microwave assistance and tested for its activity on the A375 cell line. In the new series, compounds 11a, 9d and 11b show cytotoxic activities less than second generation compounds, but similar to that of the first generation ones (IC50 = 403 nM, IC50 = 128 nM and IC50 = 584 nM, respectively). The presence of an amino acid leads to significant enhancement of the water solubility for improved drugability.


2013 ◽  
Vol 4 ◽  
Author(s):  
Bulatovic Mirna ◽  
Mojic Marija ◽  
Kaludjerovic Goran ◽  
Miljkovic Djordje ◽  
Stosic-Grujicic Stanislava ◽  
...  

Author(s):  
Florian Arendt

A test was done to see if reading a newspaper which consistently overrepresents foreigners as criminals strengthens the automatic association between foreign country and criminal in memory (i.e., implicit cultivation). Further, an investigation was done to find out if reading articles from the same newspaper produces a short-term effect on the same measure and if (1) emotionalization of the newspaper texts, (2) emotional reactions of the reader (indicated by arousal), and (3) attributed text credibility moderate the short-term treatment effect. Eighty-five participants were assigned to one of three experimental conditions. Participants in the control group received short factual crime texts, where the nationality of the offender was not mentioned. Participants in the factual treatment group received the same texts, but the foreign nationality was mentioned. Participants in the emotionalized treatment group received emotionalized articles (i.e., texts which are high in vividness and frequency) covering the same crimes, with the foreign nationality mentioned. Supporting empirical evidence for implicit cultivation and a short-term effect was found. However, only emotionalized articles produced a short-term effect on the strength of the automatic association, indicating that newspaper texts must have a minimum of stimulus intensity to overcome an effect threshold. There were no moderating effects of arousal or credibility pertaining to the impact on the implicit measure. However, credibility moderated the short-term effect on a first-order judgment (i.e., estimated frequency of foreigners of all criminals). This indicates that a newspaper’s effect on the strength of automatic associations is relatively independent from processes of propositional reasoning.


Author(s):  
Irina A. Prushkovskaya ◽  
Ira B. Tsoy

The study of diatoms in the sediments of the Amur Bay (Sea of Japan), formed over the last 2000 years, showed that the sharp short-term drops in the concentration of diatoms coincide with the minima of bromine content, which can be explained by the influence of typhoons or other catastrophic events leading to floods and used later in paleoreconstructions.


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