Acetaminophen (APAP), is a safe analgesic and antipyretic drug at therapeutic dose, and is widely used in the clinic. However, high doses of APAP can induce hepatotoxicity and nephrotoxicity. Most studies have focused on high-dose APAP-induced acute liver and kidney injury. So far, few studies have investigated the effects of the therapeutic dose (1/10 of the high dose) or of the low dose (1/100 of the high dose) of APAP on the cells. The aim of this study was to investigate the cellular effects of therapeutic- or low-dose APAP treatment on hepatoma cells and kidney fibroblasts. As expected, high-dose APAP treatment inhibited while therapeutic and low-dose treatment did not inhibit cell survival of kidney tubular epithelial cells. In addition, therapeutic-dose treatment induced an increase in the H2O2 level, activated the caspase-9/-3 cascade, and induced cell apoptosis of hepatoma cells. Notably, APAP promoted fibroblast proliferation, even at low doses. This study demonstrates that different cellular effects are exerted upon treatment with different APAP concentrations. Our results indicate that treatment with the therapeutic dose of APAP may exert an antitumor activity on hepatoma, while low-dose treatment may be harmful for patients with fibrosis, since it may cause proliferation of fibroblasts.
p -Cresyl sulfate ( p CS), a uremic toxin, can cause renal damage and dysfunction. Studies suggest that renal dysfunction increases the prevalence of renal cancer. However, the effect of p CS on the proliferation and migration of renal cancer is unclear. Clear cell renal cell carcinoma (ccRCC) expresses mutant von Hippel-Lindau gene and is difficult to treat. Hypoxia-inducible factor-1α and 2-α (HIF-1α and HIF-2α) as well as microRNA-21 (miR-21) can regulate the proliferation and migration of ccRCC cells. However, the association between HIF-α and miR-21 in ccRCC remains unclear. Therefore, the effects of p CS on ccRCC cells were investigated for HIF-α and miR-21 signals. Our results showed that p CS induced overexpression of HIF-1α and promoted the proliferation and regulated epithelial-mesenchymal transition-related proteins, including E-cadherin, fibronectin, twist and vimentin in ccRCC cells. p CS treatment increased miR-21 expression. Specifically, inhibition of miR-21 blocked p CS-induced proliferation and migration. Taken together, the present results demonstrate that p CS directly induced the proliferation and migration of ccRCC cells through mechanisms involving miR-21/HIF-1α signaling pathways.
Background/Aim: Cetrimonium bromide (CTAB), a quaternary ammonium surfactant, is an antiseptic agent against bacteria and fungi. However, the mechanisms by which its pharmacological actions affect epithelialmesenchymal transition (EMT) in hepatocellular carcinoma (HCC) cells, such as adenocarcinoma in SK-HEP-1 cells, have not been investigated. We, thereby, investigated whether CTAB inhibits cellular mobility and invasiveness of human hepatic adenocarcinoma in SK-HEP-1 cells. Materials and Methods: SK-HEP-1 cells were treated with CTAB, and subsequent migration and invasion were measured by wound healing and transwell assays. Protein expression was detected by immunoblotting analysis. Results: Our data revealed that treatment of SK-HEP-1 cells with CTAB altered their mesenchymal spindle-like morphology. CTAB exerted inhibitory effects on the migration and invasion of SK-HEP-1 cells dose-dependently, and reduced protein levels of matrix metalloproteinase-2 (MMP-2), snail, slug, twist, vimentin, fibronectin, Smad2, Smad3, Smad4, kinase (PI3K), p-PI3K, Akt, p-Akt, βcatenin, mammalian target of rapamycin (mTOR), p-mTOR, p-p70S6K, p-extracellular signal-regulated kinases (ERK)1/2, p-p38 mitogen-activated protein kinase (MAPK) and p-c-Jun N-terminal kinase (JNK), but increased protein levels of tissue inhibitor matrix metalloproteinase-1 (TIMP-1), TIMP-2, claudin-1 and p-GSK3β. Based on these observations, we suggest that CTAB not only inhibits the canonical transforming growth factor-β (TGF-β) signaling pathway though reducing SMADs (an acronym from the fusion of Caenorhabditis elegans Sma genes and the Drosophila Mad, Mothers against decapentaplegic proteins), but also restrains the non-canonical TGF-β signaling including MAPK pathways like ERK1/2, p38 MAPK, JNK and PI3K. Conclusion: CTAB is involved in the suppression of TGF-βmediated mesenchymal phenotype and could be a potent medical agent for use in controlling the migration and invasion of hepatic adenocarcinoma.Liver cancer, also known as hepatic cancer, accounts for more than 4.7 percent of all cancer cases and was ranked as the third highest mortality cause among the world's most common cancers in 2018 (8.2%) (1). Liver contain parenchymal and non-parenchymal cells (NPCs) (2). Hepatocytes are the major parenchymal cells and constitute about 80% of the liver population. Parenchymal liver cancer can be classified into two major types: i) hepatocellular carcinoma (HCC) and ii) hepatoblastoma. Non-parenchymal 3621 *These Authors contributed equally to this study.
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