Time-dependent cytotoxicity induced by SJG-136 (NSC 694501): influence of the rate of interstrand cross-link formation on DNA damage signaling. | LitMetric
Cancer Research UK Centre, The University of Edinburgh, Crewe Road South, Edinburgh EH4 2XR, United Kingdom.
Published: June 2006
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Article Abstract
SJG-136 is a new pyrrolobenzodiazepine dimer inducing time-dependent cytotoxicity. HCT 116 cells were exposed to 50 nmol/L of SJG-136 for 1 hour or 1 nmol/L of SJG-136 for 24 hours to achieve similar levels of interstrand cross-links (ICL). The short exposure led to a rapid formation of ICLs (1 hour), early H2AX foci formation (4 hours), prominent S phase arrest, and greater phosphorylation of Nbs1 (on serine 343) and Chk1 (on serine 317) than a 24-hour exposure. The prolonged exposure at low concentrations of SJG-136 induced a gradual formation of ICLs (up to 24 hours) which was associated with a limited S phase arrest and delayed Nbs1 phosphorylation. Prolonged exposure was also associated with a reduced phosphorylation of p53 on serines 15 and 20, a limited and delayed phosphorylation on serine 392, and a less prominent increase in p21 levels. These data suggest that the 24-hour exposure to a low concentration of SJG-136 led to delayed and reduced DNA damage signaling compared with a higher concentration of SJG-136 for 1 hour, resulting in greater cytotoxicity and contributing to the time-dependent cytotoxic effect of SJG-136.
The application of upconversion nanoparticles (UCNPs) for cell and tissue analysis requires a comprehensive understanding of their interactions with biological entities to prevent toxicity or harmful effects. Whereas most studies focus on cancer cells, this work addresses non-cancerous cells with their regular in vitro physiology. Since it is generally accepted that surface chemistry largely determines biocompatibility in general and uptake of nanomaterials in particular, two bilayer surface coatings with different surface shielding properties have been studied: (i) a phospholipid bilayer membrane (PLM) and (ii) an amphiphilic polymer (AP).
CD8+ T-cell abundance is insufficient to assess antitumor immunity and shows poor performance in predicting breast cancer prognosis and immunotherapy response, presumably owing to the complexity of CD8+ T-cell functionalities. While single-cell RNA sequencing (scRNA-seq) can dissect the multifaceted functions of CD8+ T cells for better immune assessment, its clinical application is limited. Herein, we developed bulk RNA-seq-based FuncDimen models from integrative analysis of scRNA-seq and matched bulk RNA-seq data, to evaluate CD8+ T-cell functionalities across 5 dimensions: tumor reactivity, cytotoxicity, IFN-γ secretion, proliferation, and apoptosis.
Ultraviolet-B (UVB) radiation is a major physical factor that induces structural changes in human skin. The aim of this study was to determine whether the novel silent information regulator 1 (sirtuin 1 SIRT1) protein activator, penilumamide, exerted any protective effects against UVB-induced skin damage using human HaCaT keratinocytes as a model. Enzymatic assays were performed to determine the SIRT1-activating ability of penilumamide, which was compared with that of resveratrol, a potent natural product SIRT1 activator with antioxidant and anti-inflammatory properties.
Background: Propylparaben (PrP) is commonly used as an antimicrobial agent in food, cosmetics, and pharmaceuticals. While recent studies have shown that PrP exposure can cause various disruptions in cellular physiology, the precise mechanisms behind these effects remain unclear.
Objective: In this study, we sought to examine the cytotoxic effects of PrP exposure on human lung cells in a dose- and time-dependent manner.
Laboratory of Parasitic Diseases, College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi Province, 030801, People's Republic of China.
Toxoplasma gondii is a common parasite in warm-blooded animals and humans, with current treatments like pyrimethamine and sulfadiazine having significant limitations, prompting a search for safer, more effective options.
This study focused on glabridin, a natural compound from a medicinal plant, finding it to be low in toxicity while effectively inhibiting T. gondii growth and altering its structure.
The results showed that glabridin improved survival rates in infected mice and affected T. gondii's metabolism, suggesting a promising new treatment avenue for this parasite.
