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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

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

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