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Specialty: Toxicology
Cancer: Liver Cancer

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Total 17 results found since Jan 2013.

Blocking autophagy by the two-pore channels antagonist tetrandrine improves sorafenib-induced death of hepatocellular carcinoma cells
Toxicol In Vitro. 2023 Apr 28:105603. doi: 10.1016/j.tiv.2023.105603. Online ahead of print.ABSTRACTSorafenib, an oral multi-kinase inhibitor, used to treat hepatocellular carcinoma (HCC). However, drug resistance is still common in several HCC patients. This complex mechanism is not yet fully elucidated, driving the search for new therapeutic targets to potentiate the antitumoral effect of sorafenib. Recent findings have linked the expression of Two-Pore Channels (TPCs) receptors with the development and progression of cancer. TPCs receptors are stimulated by NAADP, a Ca2+ messenger, and inhibited by their antagonists Ned...
Source: Toxicology in Vitro - April 30, 2023 Category: Toxicology Authors: Let ícia Paulino Sperandio Isis Valeska F Lins Adolfo G Erustes Anderson H F F Le ão Fernanda Antunes Ingrid B M Morais Heron Fernandes Vieira La ís Maria de Campos Claudia Bincoletto Soraya S Smaili Gustavo J S Pereira Source Type: research

Deregulation of signaling pathways controlling cell survival and proliferation in cancer cells alters induction of cytochrome P450 family 1 enzymes
Toxicology. 2021 Aug 14:152897. doi: 10.1016/j.tox.2021.152897. Online ahead of print.ABSTRACTCytochrome P450 family 1 (CYP1) enzymes contribute both to metabolism of xenobiotics and to the control of endogenous levels of ligands of the aryl hydrocarbon receptor (AhR). Their activities, similar to other CYPs, can be altered in tumor tissues. Here, we examined a possible role of proliferative/survival pathways signaling, which is often deregulated in tumor cells, and possible links with p300 histone acetyltransferase (a transcriptional co-activator) in the control of CYP1 expression, focusing particularly on CYP1A1. Using c...
Source: Toxicology - August 17, 2021 Category: Toxicology Authors: Martin Krko ška Jana Svobodov á Mark éta Kabátková Ond řej Zapletal Alena Hyr šlová Vaculová Jana Nekvindov á Jan Vondr áček Source Type: research

Involvement of aryl hydrocarbon receptor in the cytotoxicity of corannulene and its derivatives.
Abstract Despite numerous studies on the toxicities of planar polycyclic aromatic hydrocarbons (PAHs), very little is known about the toxicological profiles of non-planar PAHs. In the present study, the cytotoxicity of corannulene (COR), a typical bowl-shaped PAH with a myriad of applications in the area of material chemistry, and benzo[a]pyrene (BaP), a typical planar PAH with similar molecular weight, were systematically compared in various cell lines. Compared with BaP, exposure to COR resulted in less cytotoxic responses in both human (HepG2) and murine (Hepa1-6) hepatoma cells, which was characterized with a ...
Source: Toxicology Letters - December 8, 2019 Category: Toxicology Authors: Li G, Ma R, Xing Y, Wei J, Bi Y, Li C, Xiong H, Baldridge KK, Huang J, Siegel JS, Zhang Y Tags: Toxicol Lett Source Type: research

Activation of GR but not PXR by Dexamethasone Attenuated Acetaminophen Hepatotoxicities via Fgf21 Induction.
In conclusion, via GR activation, DEX induced Fgf21 expression in mouse liver and human hepatoma cells. PMID: 28088388 [PubMed - as supplied by publisher]
Source: Toxicology - January 10, 2017 Category: Toxicology Authors: Vispute SG, Bu P, Le Y, Cheng X Tags: Toxicology Source Type: research

Silver Nanoparticle-Induced Autophagic-Lysosomal Disruption and NLRP3-Inflammasome Activation in HepG2 Cells Is Size-Dependent
The objective of this study was to determine the mechanism of size- and concentration-dependent cytotoxicity of AgNPs in human liver-derived hepatoma (HepG2) cells. Mechanisms of toxicity were explored at subcytotoxic concentrations (≤10 µg/ml AgNPs) and autophagy induction, lysosomal activity, inflammasome-dependent caspase-1 activation, and apoptosis were examined. Using enhanced dark-field light microscopy, hyperspectral imaging, electron microscopy, and energy dispersive X-ray spectroscopy, AgNPs were shown to rapidly accumulate in cytoplasmic vesicles for up to 24 h and 10-nm AgNPs exhibited the highest uptak...
Source: Toxicological Sciences - March 27, 2016 Category: Toxicology Authors: Mishra, A. R., Zheng, J., Tang, X., Goering, P. L. Tags: Silver Nanoparticles, Autophagy, and Inflammation Source Type: research

Farnesoid X receptor knockdown provides significant growth inhibition in hepatocellular carcinoma cells while it does not interfere with the proliferation of primary human hepatocyte-derived cells.
Authors: Fujino T, Maruko-Ohtake A, Ohtake Y, Kobayashi T, Ando K, Takeuchi A, Ohkubo Y, Hayakawa M Abstract Identification of substances with specific toxicity for carcinoma cells promises to facilitate the development of cancer chemotherapeutics that cause minimal side effects. Here, we show that knockdown of the farnesoid X receptor (FXR) effectively suppresses the proliferation of human hepatocellular carcinoma cell lines HepG2 and HLE accompanied by elevated expression of cyclin-dependent kinase (CDK) inhibitor p16/INK4a and p21/Cip1 proteins. On the other hand, the growth of the primary human hepatocyte-deriv...
Source: Journal of Toxicological Sciences - July 15, 2015 Category: Toxicology Tags: J Toxicol Sci Source Type: research

Pifithrin-alpha has a p53-independent cytoprotective effect on docosahexaenoic acid-induced cytotoxicity in human hepatocellular carcinoma HepG2 cells.
In this report, we examined the inhibitory effects of PFT against docosahexaenoic acid (DHA)-induced cytotoxicity in the human hepatocellular carcinoma (HCC) cell line HepG2. PFT significantly abrogated DHA-induced cytotoxicity in wild-type HepG2 cells (normal expression of p53) and after p53-knockdown by siRNA, as well as in Hep3B (p53 null) and Huh7 (p53 mutant) cells. DHA-induced cytotoxicity is mediated by induction of oxidative stress, and PFT inhibited this event, but it does not exert antioxidant effects. PFT significantly suppressed the release of cytochrome c from mitochondria to cytosol, as well as changes in the...
Source: Toxicology Letters - November 18, 2014 Category: Toxicology Authors: Kanno SI, Kurauchi K, Tomizawa A, Yomogida S, Ishikawa M Tags: Toxicol Lett Source Type: research

Galangin suppresses HepG2 cell proliferation by activating the TGF-β receptor/Smad pathway.
In this study, we demonstrated that galangin induced autophagy by activating the transforming growth factor (TGF)-β receptor/Smad pathway and increased TGF-β receptor I (RI), TGF-βRII, Smad1, Smad2, Smad3 and Smad4 levels but decreased Smad6 and Smad7 levels. Autophagy induced by galangin appears to depend on the TGF-β receptor/Smad signalling pathway because the down-regulation of Smad4 by siRNA or inhibition of TGF-β receptor activation by LY2109761 blocked galangin-induced autophagy. The down-regulation of Beclin1, autophagy-related gene (ATG) 16L, ATG12 and ATG3 restored HepG2 cell proliferation and prevented gala...
Source: Toxicology - September 27, 2014 Category: Toxicology Authors: Wang Y, Wu J, Lin B, Li X, Zhang H, Ding H, Chen X, Lan L, Luo H Tags: Toxicology 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

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

Expression of glutathione peroxidase 2 is associated with not only early hepatocarcinogenesis but also late stage metastasis.
In conclusion, expression of GPX2 is associated with cancer metastasis from rat HCCs both in vitro and in vivo. Together with immunohistochemical findings of elevated expression in rat and also human liver lesions, the results point to important roles in hepatocarcinogenesis. PMID: 23867582 [PubMed - as supplied by publisher]
Source: Toxicology - July 15, 2013 Category: Toxicology Authors: Suzuki S, Pitchakarn P, Ogawa K, Naiki-Ito A, Chewonarin T, Punfa W, Asamoto M, Shirai T, Takahashi S Tags: Toxicology Source Type: research

Aryl Hydrocarbon Receptor Negatively Regulates Expression of the Plakoglobin Gene (Jup)
Plakoglobin is an important component of intercellular junctions, including both desmosomes and adherens junctions, which is known as a tumor suppressor. Although mutations in the plakoglobin gene (Jup) and/or changes in its protein levels have been observed in various disease states, including cancer progression or cardiovascular defects, the information about endogenous or exogenous stimuli orchestrating Jup expression is limited. Here we show that the aryl hydrocarbon receptor (AhR) may regulate Jup expression in a cell-specific manner. We observed a significant suppressive effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin ...
Source: Toxicological Sciences - July 10, 2013 Category: Toxicology Authors: Prochazkova, J., Kabatkova, M., Smerdova, L., Pachernik, J., Sykorova, D., Kohoutek, J., Simeckova, P., Hruba, E., Kozubik, A., Machala, M., Vondracek, J. Tags: Research Article Source Type: research