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vol. 46
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issue 3
295-308
EN
A review of the metabolic pathways and interaction with DNA of benzo(a)pyrene and some other carcinogens is presented. Consideration is given to the formation and persistens of adducts in relation to carcinogenic process.
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2002
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vol. 49
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issue 4
917-925
EN
The effect of protocatechuic acid, tannic acid and trans-resveratrol on the activity of p-nitrophenol hydroxylase (PNPH), an enzymatic marker of CYP2E1, was examined in liver microsomes from acetone induced mice. trans-Resveratrol was found to be the most potent inhibitor (IC50 = 18.5 ± 0.4 mM) of PNPH, while protocatechuic acid had no effect on the enzyme activity. Tannic acid with IC50 = 29.6 ± 3.3 mM showed mixed- and trans-resveratrol competitive inhibition kinetics (Ki = 1 mM and 2.1 mM, respectively). Moreover, trans-resveratrol produced a NADPH-dependent loss of PNPH activity, suggesting mechanism-based CYP2E1 inactivation. These results indicate that trans-resveratrol and tannic acid may modulate cytochrome P450 2E1 and influence the metabolic activation of xenobiotics mediated by this P450 isoform.
EN
The techniques applicable for identification and quantitation are critically reviewed. The review also present the data concerning an analysis of DNA adducts resulted from occupational exposure, tobacco smoking, diet and chemotherapy of tumors.
EN
The aim of this study was to evaluate the effect of niclosamide, an antihelminthic drug recently identified as potential anti-cancer agent, on head and neck squamous carcinoma cells (HNSCC) viability, cell cycle distribution and apoptosis. The expression of key components of Wnt (CTNNB1, GSK-3β, CCND1, c-MYC, MMP7, BIRC5, Axin2) and glycolysis (GLUT1, MCT1, HK2, PFKM, PKM2, PDHA1, PDK1, LDHA) pathways was also examined to assess possible involvement in niclosamide anti-carcinogenic activity. HNSCC cells (FaDu, BICR6, H314 lines) were used in the research. Niclosamide treatment affected hypopharyngeal FaDu cells to the most extent (IC50 = 0.40 µM), while H314 cells derived from the floor of mouth were the least sensitive (IC50 = 0.94 µM). In FaDu cells the increased percentage of the cells in the S phase was observed along with the induction of apoptosis. Treatment with niclosamide in FaDu cells reduced the expression of MMP7 and the majority of glycolytic genes except increased LDHA. These results indicate that niclosamide is efficient inhibitor of HNSCC cells viability, however this effect depends on the cell type. In FaDu cells, the most sensitive to its anti-proliferative effect and prone to cell cycle arrest and apoptosis, this effect might be related to slightly modulation of canonical Wnt signaling and increased expression of LDHA.
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