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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

Posttranslational mechanisms modulating the expression of the cytochrome P450 1A1 gene by methylmercury in HepG2 cells: A role of heme oxygenase-1.
In conclusion, this study demonstrated that MeHg inhibited the TCDD-mediated induction of CYP1A1 through a posttranslational mechanism and confirms the role of HO-1 in a MeHg-mediated effect. PMID: 23541843 [PubMed - in process]
Source: Toxicology Letters - May 22, 2013 Category: Toxicology Authors: Amara IE, Anwar-Mohamed A, El-Kadi AO 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

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

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