The aim of this study was to investigate the effects of plant phenolic compound tannic acid (TA) on proliferative, metastatic, invasive properties of prostate cancer (PCa) cells; PC-3 and LNCaP, as well as drug metabolizing and antioxidant enzymes. Characterization of TA was done by using FT-IR and NMR. TA dose dependently inhibited the proliferation of PC-3 and LNCaP cells with IC50 values 35.3 μM and 29.1 μM, respectively. Wound healing assay showed that TA significantly inhibited (92.7%) migration of PCa cells (p<0.0001). In addition, TA was found to have anti-invasive potential on PC-3 cells and it inhibited (80.9%, p<0.0001) invasion of PC-3 cells into matrigel. Only 17.8% of PC-3 cells can form colony in the 0.7% agarose after treatment of cells with TA at the IC50 value concentration. Furthermore, flow cytometry analyses with Annexin V-APC and 7-AAD staining demonstrated that TA increases early apoptosis rate of PC-3 cells by 25.8% and LNCaP cells by 20.9%. Besides, Western blot and qRT-PCR analyses also demonstrated that TA regulates protein and mRNA expressions of CYP17A1, CYP3A4, CYP2B6, NQO1, GSTM1 and GSTP1 enzymes. The results obtained from this study show that TA might be a good candidate for combinational therapy and highly effective strategic molecule for reducing the occurrence of PCa.

No abstract

The present study was designed to evaluate different doses of ellagic acid (EA) in vivo in rats for its potential to modulate hepatic phases I, II, and antioxidant enzymes. EA (10 or 30 mg/kg/day, intragastrically) was administered for 14 consecutive days, and activity, protein, and mRNA levels were determined. Although the cytochrome P450 (CYP) 2B and CYP2E enzyme activities were decreased significantly, the activities of all other enzymes were unchanged with the 10 mg/kg/day EA. In addition, western-blot and qRT-PCR results clearly corroborated the above enzyme expressions. On the other hand, while the NAD(P)H:quinone oxidoreductase 1 (NQO1), catalase (CAT), glutathione peroxidase (GPX), and glutathione S-transferase (GST) activities were increased significantly, CYP1A, 2B, 2C, 2E, and 19 enzyme activities were reduced significantly with 30 mg/kg/day EA. In addition, CYP2B, 2C6, 2E1, and 19 protein and mRNA levels were substantially decreased by the 30 mg/kg/day dose of EA, but the CYP1A protein, and mRNA levels were not changed. CYP3A enzyme activity, protein and mRNA levels were not altered by neither 10 nor 30 mg/kg/day ellagic acid. These results indicate that EA exerts a dose-dependent impact on the metabolism of chemical carcinogens and drugs by affecting the enzymes involved in xenobiotics activation/detoxification and antioxidant pathways.

No abstract

Cytochrome P4502E1 (CYP2E1) gene shows genetic polymorphisms that vary markedly in frequency among different ethnic and racial groups. We studied the genotype distributions and allele frequencies of three CYP2E1 polymorphisms: CYP2E1*5B (RsaI/PstI RFLP, C-1053T/G-1293C SNP, rs2031920 /rs3813867), CYP2E1*6 (DraI RFLP, T7632A SNP, rs6413432), and CYP2E1*7B (DdeI RFLP, G-71T SNP, rs6413420) by PCR/RFLP technique in a sample of 206 healthy subjects representing Turkish population. CYP2E1*5B polymorphism analysis yielded the genotype distribution as 96.12% for *1A/*1A (c1/c1), and 3.88% for *1A/*5B (c1/c2). The genotype frequencies for CYP2E1*6 polymorphism were found as 83.98% for *1A/*1A (T/T), 15.53% for *1A/*6 (T/A) and 0.49% for *6/*6 (A/A). For CYP2E1*7B (G-71T) polymorphism, the genotype frequencies were determined to be 86.89% for *1A/*1A (G/G), 12.62% for *1A/*7B (G/T) and 0.49% for *7B/*7B (T/T). Accordingly, the allele frequencies for *5B, *6 and *7B were 1.94, 8.25, and 6.80%, respectively. The genotype distributions of CYP2E1*5B and *6 in Turkish population were similar to those in other Caucasian populations, while differed significantly from East Asian populations. Recently, a novel and functionally important CYP2E1*7B polymorphism was identified in the promoter region. There have been few studies and limited data on CYP2E1*7B polymorphism frequency in the world and, so far, no information has been available for Turkish population. The genotype frequencies of CYP2E1*7B in Turkish population were found to be similar to those of other Caucasian populations. Population studies like this could be useful in assessing the susceptibility of different populations to chemical-induced diseases, including several types of cancer.