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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

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

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

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

Sanguinarine induces apoptosis in human colorectal cancer HCT-116 cells through ROS-mediated Egr-1 activation and mitochondrial dysfunction.
We examined the effects of sanguinarine, a benzophenanthridine alkaloid, on reactive oxygen species (ROS) production and the association of these effects with apoptotic cell death in a human colorectal cancer HCT-116 cell line. Sanguinarine generated ROS, which was followed by a decrease in the mitochondrial membrane potential (MMP), the activation of caspase-9 and -3, and the down-regulation of anti-apoptotic proteins, such as Bcl2, XIAP and cIAP-1. Sanguinarine also promoted the activation of caspase-8 and truncation of Bid (tBid). However, the quenching of ROS generation by N-acetyl-l-cysteine, a scavenger of ROS, rever...
Source: Toxicology Letters - May 6, 2013 Category: Toxicology Authors: Han MH, Kim GY, Yoo YH, Choi YH Tags: Toxicol Lett Source Type: research

MCM-2 is a therapeutic target of Trichostatin A in colon cancer cells.
Abstract Histone deacetylase (HDAC) inhibitors have recently emerged as a new class of anti-cancer agents. Trichostatin A (TSA), a classical HDAC inhibitor, has been demonstrated to induce cell cycle arrest, promote cell apoptosis, and inhibit metastasis. However, the molecular mechanism underlying TSA function has not been fully elucidated. In the current study, we found that TSA treatment induced altered expression of cell cycle-associated genes in HCT116 cells by RT-PCR array. Among the 84 genes related to cell cycle control, 34 genes were significantly altered by TSA treatment, with 7 genes upregulated and 27 ...
Source: Toxicology Letters - June 13, 2013 Category: Toxicology Authors: Liu Y, He G, Wang Y, Guan X, Pang X, Zhang B Tags: Toxicol Lett Source Type: research

Dichlorodiphenyltrichloroethane exposure induces the growth of hepatocellular carcinoma via Wnt/β-catenin pathway.
In this study, we evaluated the impact of p,p'-DDT on the growth of hepatocellular carcinoma using both in vitro and in vivo models. The present data indicated that the proliferation of HepG2 cells was strikingly promoted after exposed to p,p'-DDT for 4 days. In addition, reactive oxygen species (ROS) content was significantly elevated, accompanied with inhibitions of γ-glutamylcysteine synthetase (γ-GCS) and superoxide dismutase (SOD) activities. Interestingly, the levels of β-catenin and its downstream target genes (c-Myc and CyclinD1) were significantly up-regulated, and co-treatment of NAC, the ROS inhibitor, inhibi...
Source: Toxicology Letters - December 17, 2013 Category: Toxicology Authors: Jin XT, Song L, Zhao JY, Li ZY, Zhao MR, Liu WP Tags: Toxicol Lett Source Type: research

Celecoxib potentially inhibits metastasis of lung cancer promoted by surgery in mice, via suppression of the PGE2-modulated β-catenin pathway.
In conclusion, celecoxib inhibits metastasis of A549 cells in the circulation enhanced by PGE2 after surgery by not only inhibiting endogenous PGE2 expression, but also by suppression downstream of PGE2 via the GSK-3β-β-catenin pathway. PMID: 24374173 [PubMed - as supplied by publisher]
Source: Toxicology Letters - December 24, 2013 Category: Toxicology Authors: Zhang S, Da L, Yang X, Feng D, Yin R, Li M, Zhang Z, Jiang F, Xu L Tags: Toxicol Lett Source Type: research

The NF-κB family member RelB regulates microRNA miR-146a to suppress cigarette smoke-induced COX-2 protein expression in lung fibroblasts.
In this study we tested whether RelB attenuation of cigarette smoke-induced COX-2 protein is due to miR-146a. Utilizing pulmonary fibroblasts deficient in RelB expression, together with siRNA knock-down of RelB, we show the essential role of RelB in diminishing smoke-induced COX-2 protein expression despite robust activation of the canonical NF-κB pathway and subsequent induction of Cox-2 mRNA. RelB did not regulate COX-2 protein expression at the level of mRNA stability. Basal levels of miR-146a were significantly lower in Relb-deficient cells and cigarette smoke increased miR-146a expression only in Relb-expressing cell...
Source: Toxicology Letters - January 25, 2014 Category: Toxicology Authors: Zago M, de Souza AR, Hecht E, Rousseau S, Hamid Q, Eidelman DH, Baglole CJ Tags: Toxicol Lett Source Type: research

Ziyuglycoside II induces cell cycle arrest and apoptosis through activation of ROS/JNK pathway in human breast cancer cells.
In this study, the anti-proliferative effect of ziyuglycoside II in two classic human breast cancer cell lines, MCF-7 and MDA-MB-231, was extensively investigated. Our study indicated that ziyuglycoside II could effectively induce G2/M phase arrest and apoptosis in both cell lines. Cell cycle blocking was associated with the down-regulation of Cdc25C, Cdc2, cyclin A and cyclin B1 as well as the up-regulation of p21/WAF1, phospho-Cdc25C and phospho-Cdc2. Ziyuglycoside II treatment also induced reactive oxygen species (ROS) production and apoptosis by activating the extrinsic/Fas/FasL pathway as well as the intrinsic/mitocho...
Source: Toxicology Letters - March 27, 2014 Category: Toxicology Authors: Zhu X, Wang K, Zhang K, Zhu L, Zhou F Tags: Toxicol Lett Source Type: research

Nanomolar levels of PAHs in extracts from urban air induce MAPK signaling in HepG2cells.
This study has investigated intracellular MAPK signaling in response to PAHs in extracts from urban air collected in Stockholm, Sweden and Limeira, Brazil, in comparison to BP in HepG2cells. Nanomolar concentrations of PAHs in the extracts induced activation of MEK4 signaling with down-stream increased gene expression of several important stress response mediators. Involvement of the MEK4/JNK pathway was confirmed using siRNA and an inhibitor of JNK signaling resulting in significantly reduced MAPK signaling transactivated by the AP-1 transcription factors ATF2 and cJun. ATF2 was also identified as a sensitive stress respo...
Source: Toxicology Letters - June 6, 2014 Category: Toxicology Authors: Jarvis IW, Bergvall C, Morales DA, Kummrow F, Umbuzeiro GA, Westerholm R, Stenius U, Dreij K Tags: Toxicol Lett Source Type: research

Immunochemical analysis of poly(ADP-ribosyl)ation in HaCaT keratinocytes induced by the mono-alkylating agent 2-chloroethyl ethyl sulfide (CEES): impact of experimental conditions.
In conclusion, this study provides a detailed analysis of the CEES-induced PARylation response in HaCaT keratinocytes, which forms an experimental basis to study the molecular mechanism of PARP1 activation and its functional consequences after mustard treatment in general. Such a study is presented in an accompanying article (Mangerich/Debiak/Birtel et al., this issue). PMID: 26383632 [PubMed - as supplied by publisher]
Source: Toxicology Letters - September 14, 2015 Category: Toxicology Authors: Debiak M, Lex K, Ponath V, Burckhardt-Boer W, Thiermann H, Steinritz D, Schmidt A, Mangerich A, Bürkle A Tags: Toxicol Lett Source Type: research

Combined treatment with vitamin C and sulindac synergistically induces p53- and ROS-dependent apoptosis in human colon cancer cells.
In this study, we evaluated a combinatorial strategy utilizing sulindac and vitamin C. The death of HCT116 cells upon combination therapy occurred via a p53-mediated mechanism. The combination therapeutic resistance developed in isogenic p53 null HCT116 cells and siRNA-mediated p53 knockdown HCT116 cells, but the exogenous expression of p53 in p53 null isogenic cells resulted in the induction of cell death. In addition, we investigated an increased level of intracellular ROS (reactive oxygen species), which was preceded by p53 activation. The expression level of PUMA (p53-upregulated modulator of apoptosis), but not Bim, w...
Source: Toxicology Letters - June 19, 2016 Category: Toxicology Authors: Gong EY, Shin YJ, Hwang IY, Kim JH, Kim SM, Moon JH, Shin JS, Lee DH, Hur DY, Jin DH, Hong SW, Lee WK, Lee WJ Tags: Toxicol Lett Source Type: research

Involvement of HIF-1 α-regulated miR-21, acting via the Akt/NF-κB pathway, in malignant transformation of HBE cells induced by cigarette smoke extract.
Involvement of HIF-1α-regulated miR-21, acting via the Akt/NF-κB pathway, in malignant transformation of HBE cells induced by cigarette smoke extract. Toxicol Lett. 2018 Feb 28;: Authors: Lu L, Xu H, Yang P, Xue J, Chen C, Sun Q, Yang Q, Lu J, Shi A, Liu Q Abstract Although the relationship between cigarette smoke and lung cancer has been widely studied, the molecular mechanism for cigarette smoke-induced lung cancer remains largely unclear. The present study investigated the roles of hypoxia-inducible factor (HIF)-1α and miR-21 in the malignant transformation of human bronchial epithelial (HBE) ce...
Source: Toxicology Letters - February 28, 2018 Category: Toxicology Authors: Lu L, Xu H, Yang P, Xue J, Chen C, Sun Q, Yang Q, Lu J, Shi A, Liu Q Tags: Toxicol Lett Source Type: research