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2
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EN
Copper, an essential transient element, can be toxic to cells when present in excess. Altered copper homeostasis is involved in pathological events of many diseases. Human CUTA isoform2 is a member of cation tolerance protein (CutA1) family. In this study, we examined the effect of CUTA isoform2 overexpression on copper toxicity. It was shown that overexpressed CUTA isoform2 sensitized HeLa cells to copper toxicity by promoting copper-induced apoptosis. The inhibition effect of excessive copper on cell proliferation was also enhanced by overexpressed CUTA isoform2. So CUTA isoform2 was implicated to be involved in the cytotoxicity of copper.
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Camptothecin (CPT), an alkaloid natural product, extracted from Camptotheca acuminata bark, has been reported to have potential antitumor activity in diverse cancers. MicroRNAs (MiRNAs) are a class of short, non-coding RNAs that plays a crucial role in the normal physiology by attenuating translation. Here, we showed that the CPT modulates the expression of miRNAs in hepatocellular carcinoma cells (HCC). Microarray analysis reveals that CPT modulates the expression of as many as 39 miRNAs in HCC cells (Huh7), 27 miRNAs were downregulated whereas 12 miRNAs were upregulated. miR-16 is the key miRNA upregulated by CPT and targets key prosurvival proteins (MMP-2, MMP-9 and cyclin D1). Our results demonstrate that CPT is inhibiting cell viability of HCC cells significantly when compared with the untreated cells. Wound healing and colony formation assay confirm inhibition of cell migration and clonogenic property of Huh7 cells respectively, upon the dose-dependent treatment of CPT. Furthermore, the Boyden chamber assay analysis revealed a significant inhibition of number of invasive cells in CPT treated cells with comparison to untreated Huh7 cells. Mechanistically, CPT upregulates miR-16 expression which targets MMP-2, MMP-9, cyclin D1 downregulation and subsequently upregulates the expression of E-cadherin, TIMP1, p21, and p27, thereby inhibits cell migration, invasion and clonogenic property of HCC cells. In summary, CPT treatment in Huh7 cells decreases cell viability and upregulates miR-16 expression, which results in inhibition of cell migration, invasion and clonogenic property of cells, by decreasing MMP-2, MMP-9, cyclin D1 and increasing the expression of cell cycle-regulated proteins p21 and p27.
EN
Occupational exposures to environmental toxicants have been associated with the onset of skin lesions-including cancers. Identification and reduction of exposure to such compounds is an important public health goal. We examined the effect of cashew shell oil (CSO), used in skin tattooing for its potential to induce skin transformation in rats. Corn oil and CSO (25, 50, and 100%) were topically applied to depilated sections of Wistar' rat skin (groups: I-IV) for six weeks. Effect of treatments on serum transaminases activity, histological changes in hepatocytes and induction of micronuclei in the bone marrow were examined. In addition, CSO-induced hepatocyte proliferation was also quantified. All animals survived the course of the study. Reduced percentage change in body weight and physical trauma were observed in CSO-treated rat. The effects were more prominent in Group IV (100% CSO). Relative liver weights and number of hepatocytes (cells/mm2) increased significantly in groups II-IV relative to control (p < 0.05). Serum transaminases activities were not significantly (p > 0.05) affected in treated groups. Hepatic histopathology revealed moderate sinusoidal congestion (group II), in addition to portal congestion in (group III), with mononuclear cellular infiltration (group IV) animals. In addition, CSO induced significant micronuclei formation of polychromatic erythrocyte (mPCEs) in the rat bone marrow (p < 0.05) when compared with control. Topical application of CSO disrupted skin cells integrity resulting in physical trauma. In addition, CSO appears to be clastogenic and induces hepatocyte proliferation. Occupational exposure to CSO especially for engraving tattoos in humans should be discouraged and further studies need to be conducted.
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Content available remote Targeting clusterin in prostate cancer
75%
EN
The exposure to extremely low frequency electromagnetic field (ELF-MF, frequencies less than 200-300 Hz) can alter the transcription and translation of genes, influence the cell proliferation rate and affect enzyme activities. Moreover, the hypothesis that ELF-MF increases free oxygen metabolites generation has been proposed. Since recent in vivo studies suggest that electric and magnetic fields are able to affect adipose cells metabolism. The aim of the study was to examine the effects of ELF-MF (frequency of basic impulse 180-195 Hz, induction 120 µT) on cell proliferation, antioxidative enzyme activities and malondialdehyde (MDA) concentration in 3T3-L1 preadipocyte cell culture. We found that ELF-MF application lasting 36 minutes daily failed to influence cell count after 24h and 48 h of incubation. After 24 h, in the ELF-MF treated group, manganese- and copper-zinc-containing superoxide dismutase (MnSOD and Cu/ZnSOD) isoenzymes media activities were decreased, catalase activity was increased, whereas there were no significant differences in glutathione peroxidase (GSH-Px) and glutathione reductase (GSSG-Rd) activities in comparison to the control. After 48 h of incubation, all enzyme activities were reduced, except for GSSG-Rd, in which no changes were noticed. MDA concentration at 24 h after incubation with the exposure to ELF-MF was significantly higher in comparison to the control, without ELF-MF. After 48 h of incubation, MDA levels were significantly lower in both groups with no differences between the groups without and with ELF-MF. We conclude that ELF-MF influences antioxidative enzyme activities and increases lipid peroxidation in 3T3-L1 preadipocyte cultures.
EN
The influence of an antiestrogen, indole-3-carbinol (I3C) on the expression of CYP1A1, CYP1B1 and AhR genes was investigated in an attempt to establish whether I3C could increase the expression of genes involved in estrone metabolism. Another purpose was to examine the proliferation of an estrogen-dependent breast cancer cell (MCF-7 line) under the influence of I3C and both I3C and DDT. In MCF-7 cells incubated with I3C or I3C and DDT combined, quantitative RT-PCR analysis revealed a significant increase in the level of CYP1A1, AhR, and CYP1B1 transcripts. The proliferation rate of MCF-7 cells was increased by treatment with DDT or estradiol (E2), whereas I3C did not affect the proliferation of MCF-7 cells but greatly reduced the stimulatory effect of DDT, and abolished the effect of E2. The level of p21 transcript, encoding p21 protein involved in the cell cycle, was increased several-fold by I3C comparing to its level in cells incubated with estradiol or DDT. The results suggest that the proliferation of MCF-7 cells is accompanied not only by expression of genes encoding cytochromes involved in estrogen metabolism, but also by changes in the expression of other genes including that encoding p21 protein involved in the cell cycle.
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In the human body, stem cells are located in niches, which are extremely complex microenvironments (with specified oxygen conditions and cellular together with extracellular matrix components arranged as a 3D structure). The influence of signals from niches seems to play an important role in maintenance of stem cells pluripotency and in their differentiation. We have been investigating the influence of the different niche components on the proliferation and differentiation of neural stem cells into specific cell types as well as the molecular mechanisms underlying this cell responses. In this study we are investigating the influence of low oxygen tension conditions on proliferation and differentiation of Human Umbilical Cord Blood of Neural Stem Cell (HUCB-NSC). Human Neural Stem Cells (NSC) in their physiological niches are exposed to 2–8% oxygen level. For that purpose, HUCB-NSC, were cultivated in two oxygen tension conditions: 21% and 5% with or without the presence of differentiation factor dBcAMP (N6,2′-O-Dibutyryladenosine 3′,5′-cyclic monophosphate sodium salt). We compared the expression of the markers characteristic for proliferation (Ki67) as well as neuronal and astroglial lineage commitment (MAP2, GFAP, β-tubulin, NF200). The presence of tested markers was revealed on the protein (immunocytochemistry) and gene expression level (Real-Time PCR). Our data show, that the low oxygen tension promote HUCB-NSC differentation into neuronal lineage. We also observed that low concentration of oxygen increases cell proliferation.Sponsored by grant from Polish Ministry of Scientific Research and Higher Education No 5978/B/PO1/2010/38
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Effects of angiotensins II (AngII), angiotensin IV (AngIV, 3-8 fragment of angiotensin II) and losartan (an antagonist of angiotensin receptor type 1) on the proliferation of adrenocortical cells in ovariectomized rats have been studied. The incorporation of bromodeoxyuridine (BrdU) into cell nuclei was used as an index of cell proliferation. AngIV decreased BrdU labeling index mainly in the reticularis zone and losartan (Los) was able to partially reverse this inhibitory effect of AngIV. AngII had no effect on the adrenocortical cell proliferation when given alone, however Los given simultaneously diminished BrdU incorporation into nuclei of glomerulosa and reticularis zones as compared with AngII. These findings suggest that AngII and AngIV modulate adrenocortical cell proliferation in ovariectomized rats.
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The aim of our study was an evaluation of the expression of cell proliferation markers (PCNA and Ki-67) in conjunctival and eyelid papillomas and squamous and basal cell cancers. A series of 9 cases of squamous cell cancer (SCC), 15 cases of basal cell cancer (BCC) and 43 cases of squamous cell papilloma (SCP) were assessed using the immunohistochemical method with monoclonal antibodies. PCNA overexpression was observed in 100% of SCP, in 88.8% of SCC and in 100% of BCC cases. Ki-67 overexpression was seen in 32.5% of cases of SCP, in 22.2% of SCC and in 66.6% of BCC. The results showed that an evaluation of Ki-67 expression is the most valuable cell proliferation marker.
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