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Source: Toxicology Letters

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Total 86 results found since Jan 2013.

Assessment of drug delivery and anticancer potentials of nanoparticles-loaded siRNA targeting STAT3 in lung cancer, in vitro and in vivo.
Abstract Activation of signal transducer and activator of transcription3 (STAT3) is a hallmark of several types of cancer. Failure to inhibit STAT3 expression by injection of siRNA for STAT3 directly to Balb/c mice led us to adopt alternative means. We formulated nanoparticle-based encapsulation of siRNA (NsiRNA) with polyethylenimine (PEI) and poly (lactide-co-glycolide) (PLGA) and characterized them. The siRNA treated and NsiRNA-treated cells were subjected separately to different assay systems. We also checked if NsiRNA could cross the Blood Brain Barrier (BBB). Cell viability reduced dramatically in A549 cells...
Source: Toxicology Letters - January 16, 2014 Category: Toxicology Authors: Das J, Das S, Paul A, Samadder A, Bhattacharyya SS, Khuda-Bukhsh AR Tags: Toxicol Lett Source Type: research

Smad3 mediates cigarette smoke extract (CSE) induction of VEGF release by human fetal lung fibroblasts.
Abstract Cigarette smoke is the major cause of chronic obstructive pulmonary disease (COPD), yet pathogenic mechanisms are not fully understood. Vascular endothelial growth factor (VEGF) is one of the major regulators of endothelial cell survival and is believed to play a role in the pathogenesis of COPD. Fibroblasts are a significant source of VEGF in the lungs; however the effect of cigarette smoke exposure on VEGF release by fibroblasts is not fully understood. We hypothesized that cigarette smoke-induced disturbed VEGF release by human lung fibroblasts is a potential pathogenic mechanism that could contribute ...
Source: Toxicology Letters - April 22, 2013 Category: Toxicology Authors: Farid M, Kanaji N, Nakanishi M, Gunji Y, Michalski J, Iwasawa S, Ikari J, Wang X, Basma H, Nelson AJ, Liu X, Rennard SI Tags: Toxicol Lett Source Type: research

Par-4 Downregulation Confers Cisplatin Resistance in Pancreatic Cancer Cells via PI3K/Akt Pathway-dependent EMT.
In conclusion, these results indicate that Par-4 downregulation confers CDDP resistance via PI3K/Akt pathway-dependent EMT in BXPC-3 cells. Therefore, Par-4 may be a potential target for overcoming CDDP resistance in pancreatic cancer. PMID: 24144893 [PubMed - as supplied by publisher]
Source: Toxicology Letters - October 18, 2013 Category: Toxicology Authors: Tan J, You Y, Xu T, Yu P, Wu D, Deng H, Zhang Y, Bie P Tags: Toxicol Lett Source Type: research

Involvement of CTR1 and ATP7A in Lead (Pb)-induced Copper (Cu) Accumulation in Choroidal Epithelial Cells.
This study investigated the roles of Cu transporter 1 (CTR1) and ATP7A, two Cu transporters, in Pb-induced Cu accumulation in the choroidal epithelial cells. Pb exposure resulted in increased intracellular (64)Cu retention, accompanying with up-regulated CTR1 level. Knockdown of CTR1 using siRNA before Pb exposure diminished the Pb-induced increase of (64)Cu uptake. The expression level of ATP7A was down-regulated following the Pb exposure. ATP7A siRNA knockdown, or PCMB treatment, inhibited the (64)Cu efflux from the cells, while the following additional incubation with Pb failed to further increase the intracellular (64)...
Source: Toxicology Letters - December 5, 2013 Category: Toxicology Authors: Zheng G, Zhang J, Xu Y, Shen X, Song H, Jing J, Luo W, Zheng W, Chen J Tags: Toxicol Lett Source Type: research

Downregulation of Rad51 participates in OTA-induced DNA double-strand breaks in GES-1 cells in vitro.
Abstract Ochratoxin A (OTA), a mycotoxin produced by ubiquitous Aspergilli, is carcinogenic, teratogenic, and nephrotoxic in both humans and animals. Our previous study found that OTA induced DNA double-strand breaks (DSBs) and resulted in G2 phase arrest in human gastric epithelium immortalized (GES-1) cells. DSBs can cause genomic instability, mutations, and neoplastic transformations, and improper repair of DSBs may lead to the development of cancer. Rad51 is a key protein in the homologous recombination (HR) pathway of DSBs repair. The roles of Rad51 in the repair of DNA damage vary in response to different ty...
Source: Toxicology Letters - February 10, 2014 Category: Toxicology Authors: Lian H, Cui J, Wang Y, Liu J, Wang J, Shen H, Xing L, Wang J, Yan X, Zhang X Tags: Toxicol Lett Source Type: research

Anacardic acid induces cell apoptosis associated with induction of ATF4-dependent endoplasmic reticulum stress.
Abstract Anacardic acid (6-pentadecylsalicylic acid, AA), a natural compound isolated from the traditional medicine Amphipterygium adstringens, has been reported to possess antitumor activities. However, its molecular targets have not been thoroughly studied. Here, we report that AA is a potent inducer of endoplasmic reticulum (ER) stress, leading to apoptosis in hepatoma HepG2 and myeloma U266 cells. Induction of ER stress by AA was supported by a dose- and time-dependent increase in expression of the ER signaling downstream molecules, such as GRP78/BiP, phosphorylated eIF2α, ATF4 and CHOP in both HepG2 and U266...
Source: Toxicology Letters - May 19, 2014 Category: Toxicology Authors: Huang H, Hua X, Liu N, Li X, Liu S, Chen X, Zhao C, Lan X, Yang C, Dou QP, Liu J Tags: Toxicol Lett Source Type: research

GAPDH-knockdown reduce rotenone-induced H9C2 cells death via autophagy and anti-oxidative stress pathway.
CONCLUSION: siRNA-mediated GAPDH knockdown reduced rotenone-induced H9C2 cell death occurring via autophagy and anti-oxidative stress pathway. This study enriches the understanding of GAPDH pathophysiology role, and provides potential new therapeutic targets for cardiac disease states characterized by oxidative stress. PMID: 25725130 [PubMed - as supplied by publisher]
Source: Toxicology Letters - February 25, 2015 Category: Toxicology Authors: Liang S, Figtree G, Aiqun M, Ping Z Tags: Toxicol Lett Source Type: research

The IL-6/STAT3 pathway via miR-21 is involved in the neoplastic and metastatic properties of arsenite-transformed human keratinocytes.
Abstract Inflammation and microRNAs are involved in human skin cancer; however, their molecular mechanisms remain unclear. Further, a concern in skin cancer research is the identification of biomarkers for early diagnosis and accurate prognosis. To explore new biomarkers of chemical exposure in risk assessment of chemical carcinogenesis and arsenite-induced skin cancer, we investigated the roles of interleukin-6 (IL-6) regulation of microRNA-21 (miR-21), functioning via activation of signal transducers and activators of transcription 3 (STAT3), in neoplastic and metastatic properties of immortalized human keratino...
Source: Toxicology Letters - June 20, 2015 Category: Toxicology Authors: Lu X, Luo F, Liu Y, Zhang A, Li J, Wang B, Xu W, Shi L, Liu X, Lu L, Liu Q Tags: Toxicol Lett Source Type: research

Transient Receptor Potential Melastatin 4 Contributes to Early-Stage Endothelial Injury Induced by Arsenic Trioxide.
CONCLUSION: TRPM4 is involved in endothelial injury induced by ATO and may be a promising therapeutic target for endothelial injury. PMID: 31054354 [PubMed - as supplied by publisher]
Source: Toxicology Letters - April 30, 2019 Category: Toxicology Authors: Yu CX, Zhang YY, Wu XY, Tang HX, Liang XQ, Xue ZM, Xue YD, Li J, Zhu H, Huo R, Ban T Tags: Toxicol Lett Source Type: research

Induction of lipid droplets in THP-1 macrophages by multi-walled carbon nanotubes in a diameter-dependent manner: a transcriptomic study.
In conclusion, the results of this study revealed the induction of LDs by MWCNTs in a diameter-dependent manner through the activation of PPAR signalling pathway. PMID: 32649966 [PubMed - as supplied by publisher]
Source: Toxicology Letters - July 6, 2020 Category: Toxicology Authors: Yang T, Chen J, Gao L, Huang Y, Liao G, Yi C Tags: Toxicol Lett Source Type: research

Regulation of CRMP2 by Cdk5 and GSK-3 β Participates in Sevoflurane-induced Dendritic Development Abnormalities and Cognitive Dysfunction in Developing Rats.
CONCLUSION: Cdk5/CRMP2 and GSK-3β/CRMP2 pathways participate in sevoflurane-induced dendritic development abnormalities and cognitive dysfunction in developing rats. PMID: 33548343 [PubMed - as supplied by publisher]
Source: Toxicology Letters - February 3, 2021 Category: Toxicology Authors: Liao Z, Huang Z, Li J, Li H, Miao L, Liu Y, Zhang J, Xu Y, Li Y Tags: Toxicol Lett Source Type: research

Tyrphostin AG1024 downregulates aryl hydrocarbon receptor (AhR) expression in an IGF1R and IR-independent manner
In this study, we screened for important molecules for AhR activation using SCAD inhibitor kits. Among 164 kinase inhibitors listed in these kits, tyrphostin AG1024, commonly used as an inhibitor of insulin-like growth factor receptor (IGF1R) and insulin receptor (IR), was identified as a potent inhibitor of 3-methylcholanthrene (MC)-mediated AhR activation. We further investigated the mechanism by which AG1024 suppresses MC-mediated AhR activation. AG1024 decreased AhR-dependent luciferase activity, CYP1A1 gene expression, and its protein expression. However, when IGF1R siRNA and IR siRNA were used, AhR activation was sli...
Source: Toxicology Letters - February 12, 2022 Category: Toxicology Authors: Shunsuke Tomita Kazuho Inaba Masashi Sekimoto Source Type: research