deoxycholic-acid has been researched along with Carcinoma--Squamous-Cell* in 9 studies
9 other study(ies) available for deoxycholic-acid and Carcinoma--Squamous-Cell
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Preparation of Oxaliplatin-Deoxycholic Acid Derivative Nanocomplexes and In Vivo Evaluation of Their Oral Absorption and Tumor Growth Suppression.
To prepare orally available oxaliplatin (OXA), nanocomplexes were formed by ionic conjugation of OXA with the deoxycholic acid derivative, Nalpha-deoxycholy-L-lysyl-methylester (DCK), as an oral absorption enhancer. We characterized the DCK-conjugated OXA nanocomplexes by differential scanning calorimetry, particle size determination, and morphological analysis. To evaluate the effects of DCK on the intestinal permeability of OXA, we assessed the solubilities and partition coefficients of OXA and the OXA/DCK nanocomplex, and then conducted in vitro artificial intestinal membrane and Caco-2 cell permeability studies. Finally, bioavailability in rats and tumor growth inhibition in the squamous cell carcinoma (SCC7) model after oral administration of the OXA/DCK nanocomplex were investigated compared to pure OXA. Analysis of the ionic complex formation of OXA with DCK revealed that OXA existed in an amorphous form within the complex, resulting in for- mation of nanocomp;exes (35.05 +/- 4.48 nm in diameter). The solubility of OXA in water was approximately 7.07 mg/mL, whereas the water solubility of OXA/DCK was approximately 2.04 mg/mL and its partition coefficient was approximately 1.2-fold higher than that of OXA. The in vitro intestinal membrane permeability of OXA was significantly enhanced by complex formation with DCK. An in vivo pharmacokinetic study revealed that the Cm value of the OXA/DCK nanocomplex was 3.18-fold higher than that of OXA (32.22 +/- 10.24 ng/mL), and the resulting oral bioavailability of the OXA/DCK nanocomplex was 39.3-fold more than that of OXA. Furthermore, the oral administration of OXA/DCK significantly inhibited tumor growth in SCC7-bearing mice, and maximally inhibited tumor volume by 54% compared to the control. These findings demonstrate the therapeutic potential of the OXA/DCK nanocomplex as an oral anti-cancer therapy because it improves the oral absorption of OXA, which may improve patient compliance and expand the therapeutic applications of OXA to the prevention of recurrence and metastasis. Topics: Animals; Caco-2 Cells; Carcinoma, Squamous Cell; Deoxycholic Acid; Drug Screening Assays, Antitumor; Humans; Mice; Nanoparticles; Oral Mucosal Absorption; Organoplatinum Compounds; Oxaliplatin; Rats | 2016 |
Investigating the pathogenic role of PADI4 in oesophageal cancer.
PADI4 post-translationally converts peptidylarginine to citrulline. PADI4 can disrupt the apoptotic process via the citrullination of histone H3 in the promoter of p53-target genes. The current study focused on PADI4 expression in various subtypes of oesophageal carcinoma (EC) by immunohistochemistry, western blotting and real time PCR. The study also investigated the effect of bile acid deoxycholate (DCA) on PADI4 expression in Eca-109 cells that originated from EC. Apoptosis and DCA-induced toxicity were analyzed by TUNEL, MTT assay and flow cytometry. Additionally, the present study investigated the correlation between single nucleotide polymorphism (SNP) in PADI4 gene and EC risk in Chinese population using Illumina GoldenGate assay. Compared with paraneoplastic tissues, the transcriptional and translational levels of PADI4 were significantly elevated in oesophageal squamous cell carcinoma (ESCC, n=9) and oesophageal adenocarcinoma (EAC, n=5) tissues. Immunolabeling detected expression of PADI4 in ESCC tissues (98.56%, n=139), EAC samples (87.5%, n=16) and oesophageal small cell undifferentiated carcinoma (91.7%, n=12) but not in normal tissues (0%, n=16). Furthermore, PADI4 levels is positively correlated with the pathological classification of ESCC (p=0.009). PADI4 expression levels were consistent with the number of apoptotic cells in the induced Eca-109 cells. rs10437048 [OR= 0.012831; 95% CI, 0.001746~0.094278; p=1.556×10(-12)] were significantly associated with decreased risk of EC, whereas rs41265997 [OR=12.7; 95% CI, 0.857077~33.207214; p=3.896×10(-8)] were significantly associated with increased risk of EC. rs41265997 in exon 3 of PADI4 gene is non-synonymous and converts ACG to ATG resulting in a threonine /methionine conversion at position 274 of the protein. Haplotypes GC that carries the variant alleles for rs2501796 and rs2477134 was significantly associated with increased risk of EC (frequency=0.085, p=0.0256, OR=2.7). The results suggest that PADI4 expression is related to the tumorigenic process of EC and the DCA-induced apoptosis. The PADI4 gene may be a valid EC susceptibility gene. Topics: Adenocarcinoma; Apoptosis; Asian People; Blotting, Western; Carcinoma, Squamous Cell; Case-Control Studies; Cell Line, Tumor; Cell Proliferation; China; Deoxycholic Acid; Esophageal Neoplasms; Esophagus; Female; Genetic Predisposition to Disease; Haplotypes; Humans; Hydrolases; Male; Middle Aged; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Protein-Arginine Deiminase Type 4; Protein-Arginine Deiminases | 2011 |
Antiangiogenic activity of orally absorbable heparin derivative in different types of cancer cells.
Orally absorbable anticancer medications have great advantages for conventional cancer therapies to patients. Here we evaluated the potent anticancer effect of orally absorbable LHD, a chemical conjugate of low-molecular-weight heparin and deoxycholic acid, on tumor graft growth models.. We characterized the angiogenic factors, such as VEGF, heparanase, and MMPs, of murine squamous cell carcinoma (SCC7), melanoma (B16F10) or lung carcinoma (LLC1). Two weeks after oral administration of LHD into these cancer-cell-bearing mice, we evaluated the antiangiogenic activity of LHD.. Although all cancer cells expressed the angiogenic factors, SCC7 cells had much higher angiogenic potential and grew rapidly after implantation into mice. When orally administered, LHD delayed tumor graft growth regardless of cancer types. Particularly, LHD powerfully diminished the SCC7-derived tumor growth. Also, the expression of angiogenic factors in all kinds of tumor tissues was decreased, thereby attenuating the neovascularization in tumor tissue.. Our study shows that LHD has potent anticancer and antiangiogenic effect on at least three kinds of tumor cells. LHD can be specifically used for preventing neovascularization in tumor tissue because it has therapeutical potential as an antiangiogenic drug and can be orally absorbed. Topics: Absorption; Administration, Oral; Angiogenesis Inhibitors; Animals; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Proliferation; Deoxycholic Acid; Disease Models, Animal; Heparin, Low-Molecular-Weight; Humans; Immunohistochemistry; Lung Neoplasms; Melanoma; Mice; Mice, Inbred C57BL; Molecular Structure | 2009 |
Combination therapy of heparin-deoxycholic acid conjugate and doxorubicin against squamous cell carcinoma and B16F10 melanoma.
Our previous study confirmed that heparin-deoxycholic acid conjugate (HD) had a potent antiangiogenic effect and safety to use for long-term treatment. Herein, the combined therapeutic effect of HD and doxorubicin (DOX) was evaluated against squamous cell carcinoma (SCC7) and B16F10 melanoma.. The inhibitory effect of cell proliferation and cellular uptake of HD was studied in SCC7 and B16F10. The combination effects of HD and DOX were evaluated by measuring cytotoxicity and apoptosis as well as tumor growth and apoptosis in vivo against SCC7 and B16F10 tumor-bearing mice.. HD displayed potent inhibitory effect on SCC7 and B16F10 cell proliferation, but it showed a low cytotoxic effect. Concurrent treatment of HD and DOX displayed enhanced cytotoxic effects and apoptosis on SCC7 and B16F10. The cellular uptake of HD and DOX was affected by the collective cytotoxic effects of these two drugs: each drug suppressed the tumor growth, and their combined treatment enhanced apoptosis and collectively inhibited the tumor growth of SCC7 and B16F10 in vivo.. These results demonstrated that HD with cytostatic and antiangiogenetic activities, enhanced the antitumor activity of DOX against SCC7 and B16F10, and the combined treatment of these two drugs might have enhanced therapeutic efficacy. Topics: Animals; Apoptosis; Carcinoma, Squamous Cell; Deoxycholic Acid; Doxorubicin; Flow Cytometry; Heparin; Male; Melanoma, Experimental; Mice; Mice, Inbred C3H; Mice, Inbred C57BL | 2008 |
Deoxycholic acid at neutral and acid pH, is genotoxic to oesophageal cells through the induction of ROS: The potential role of anti-oxidants in Barrett's oesophagus.
Bile acids are often refluxed into the lower oesophagus and are candidate carcinogens in the development of oesophageal adenocarcinoma. We show here that the secondary bile acid, deoxycholic acid (DCA), is the only one of the commonly refluxed bile acids tested here, to show genotoxicity, in terms of chromosome damage and mutation induction in the human p53 gene. This genotoxicity was apparent at both neutral and acidic pH, whilst there was a considerable increase in bile-induced toxicity at acidic pH. The higher levels of cell death and low cell survival rates at acidic pH may imply that acid bile exposure is toxic rather than carcinogenic, as dead cells do not seed cancer development. We also show that DCA (at neutral and acid pH) induced the release of reactive oxygen species (ROS) within the cytoplasm of exposed cells. We further demonstrate that the genotoxicity of DCA is ROS mediated, as micronucleus induction was significantly reduced when cells were treated with DCA + the anti-oxidant vitamin C. In conclusion, we show that DCA, is an effective genotoxin at both neutral and acidic pH. As bile acids like DCA can induce DNA damage at neutral pH, suppressing the acidity of the refluxate will not completely remove its carcinogenic potential. The genotoxicity of DCA is however, ROS dependent, hence anti-oxidant supplementation, in addition to acid suppression may block DCA driven carcinogenesis in Barrett's patients. Topics: Adenocarcinoma; Antioxidants; Ascorbic Acid; Barrett Esophagus; Carcinoma, Squamous Cell; Cell Survival; Deoxycholic Acid; Detergents; DNA Damage; Esophageal Neoplasms; Humans; Hydrogen-Ion Concentration; Micronucleus Tests; Reactive Oxygen Species; Tumor Cells, Cultured; Tumor Suppressor Protein p53 | 2007 |
The effect of alginates on deoxycholic-acid-induced changes in oesophageal mucosal biology at pH 4.
Long-standing gastro-oesophageal reflux disease (GORD) can give rise to Barrett's oesophagus (BM), a metaplastic condition and precursor to oesophageal adenocarcinoma (AC). Oesophageal cancer was once rare but is now the 5th biggest cancer killer in the U.K. Reflux of bile acids into the oesophagus is implicated in the progression to BM as bile acids at pH 4 have been shown to induce c-myc expression, an oncogene upregulated in BM and AC. In the present study we investigated the role of the biopolymer alginate on bile acid induced molecular changes in oesophageal cell lines. OE21, OE33 and TE-7 oesophageal cell lines were exposed to 100 microM deoxycholic acid at pH 4 in the presence or absence of alginates. Levels of c-myc, E-cadherin, beta-catenin and Tcf signalling were determined by Real-Time PCR, Western blotting, immunofluoresence and reporter assays. All alginates tested were able to prevent the induction of c-myc by acidified deoxycholic acid in vitro. The upstream effects of acidified deoxycholic acid on E-cadherin, beta-catenin and Tcf signalling were also suppressed by alginate. Therefore, we have demonstrated that reflux of bile acids into the oesophagus initiates a potentially damaging molecular cascade of events using an in vitro model and that a biopolymer, alginate, can protect against these effects. Topics: Alginates; Carcinoma, Squamous Cell; Cell Differentiation; Cell Line, Tumor; Deoxycholic Acid; Esophageal Neoplasms; Esophagus; Humans; Hydrogen-Ion Concentration; Mucous Membrane | 2007 |
Downregulation of p63 upon exposure to bile salts and acid in normal and cancer esophageal cells in culture.
p63 is a member of the p53 protein family that regulates differentiation and morphogenesis in epithelial tissues and is required for the formation of squamous epithelia. Barrett's mucosa is a glandular metaplasia of the squamous epithelium that develops in the lower esophagus in the context of chronic, gastroesophageal reflux and is considered as a precursor for adenocarcinoma. Normal or squamous cancer esophageal cells were exposed to deoxycholic acid (DCA, 50, 100, or 200 microM) and chenodeoxycholic and taurochenodeoxycholic acid at pH 5. p63 and cyclooxygenase-2 (COX-2) expressions were studied by Western blot and RT-PCR. DCA exposure at pH 5 led to a spectacular decrease in the levels of all isoforms of the p63 proteins. This decrease was observed within minutes of exposure, with a synergistic effect between DCA and acid. Within the same time frame, levels of p63 mRNA were relatively unaffected, whereas levels of COX-2, a marker of stress responses often induced in Barrett's mucosa, were increased. Similar results were obtained with chenodeoxycholic acid but not its taurine conjugate at pH 5. Proteasome inhibition by lactacystin or MG-132 partially blocked the decrease in p63, suggesting a posttranslational degradation mechanism. These results show that combined exposure to bile salt and acid downregulates a critical regulator of squamous differentiation, providing a mechanism to explain the replacement of squamous epithelium by a glandular metaplasia upon exposure of the lower esophagus to gastric reflux. Topics: Acetylcysteine; Apoptosis; Barrett Esophagus; Carcinoma, Squamous Cell; Cell Line, Tumor; Cells, Cultured; Chenodeoxycholic Acid; Cyclooxygenase 2; Deoxycholic Acid; DNA-Binding Proteins; Down-Regulation; Doxorubicin; Esophageal Neoplasms; Esophagus; Fluorescent Antibody Technique; Humans; Hydrogen-Ion Concentration; Leupeptins; Proteasome Inhibitors; Taurochenodeoxycholic Acid; Trans-Activators; Transcription Factors; Tumor Suppressor Proteins | 2007 |
Heparin-deoxycholic acid chemical conjugate as an anticancer drug carrier and its antitumor activity.
A chemically modified heparin-DOCA (HD) conjugate was developed as a drug carrier for cancer therapy. HD conjugate was found to have markedly low anticoagulant activity and to form self-assembled nanoparticles in aqueous condition. We observed that HD conjugate prevented squamous cell carcinoma (SCC) and human umbilical vascular endothelial cell (HUVEC) proliferation during BrdU incorporation assays. Here, we prepared doxorubicin-loaded heparin nanoparticles by entrapping doxorubicin into the amphiphilic HD conjugate by physical interaction and characterized the properties of these nanoparticles using Dynamic Light Scattering (DLS) and Atomic Force Microscope (AFM). In this study, doxorubicin-loaded heparin nanoparticles were designed to improve the antitumor effects of nano-sized particles (range of 180 to 210 nm) at high drug-loading efficiencies in the range 64% to 96%. These doxorubicin-loaded heparin nanoparticles displayed sustained drug release patterns. It was confirmed in vivo toxicity studies that HD conjugate did not induce unexpected side effects and that DHN 20 was safer than free DOX. An in vivo study showed that HD conjugate, doxorubicin and DHN 20 (one of doxorubicin-loaded heparin nanoparticles) induced tumor volume reductions of 43%, 56% and 74%, respectively, relative to the saline treated control. These results suggest that the drug-entrapped with heparin nanoparticles might provide a novel therapy for SCC. Topics: Animals; Antibiotics, Antineoplastic; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Proliferation; Deoxycholic Acid; Doxorubicin; Drug Carriers; Heparin; Male; Mice; Mice, Inbred C3H; Nanostructures | 2006 |
Sulphated bile acid per se inhibits colonic carcinogenesis in mice.
Peroral sulpholithocholic acid (SLC) promoted colonic tumorigenesis in conventional rats. We then tested this compound in the mouse, a species with different bile acid metabolism from the rat. Female conventional ICR mice received 0.5 mg of N-methyl-N-nitrosourea (MNU) three times in one week intrarectally or 16 mg/kg body weight of 1,2-dimethylhydrazine (DMH) subcutaneously once a week for 10 weeks, followed by a basal diet (CE-2), or CE-2 containing SLC or lithocholic acid (LC) (both at 0.5 mmol/100 g CE-2) for 40 weeks. At autopsy, numbers of mice bearing colonic neoplasms were 4/26 (15%) in the MNU + CE-2, 4/23 (17%) in the MNU + SLC, 5/28 (18%) in the MNU + LC, 12/24 (50%) in the DMH + CE-2, 6/23 (26%) in the DMH + SLC and 11/27 (41%) in the DMH + LC group. The DMH + SLC group had less adenocarcinomas than did the DMH + CE-2 and the DMH + LC group (P < 0.05). Total faecal bile acids in the mice fed on bile salts showed threefold increases compared with those on the basal diet. Sulphates constituted an average 7% and 19% of faecal bile acids in the MNU + SLC and DMH + SLC group, respectively. These results indicated that effects of peroral SLC on colonic carcinogenesis correlated with the degree of desulphation of SLC in the intestine and sulphates per se inhibited colonic carcinogenesis. Topics: 1,2-Dimethylhydrazine; Adenocarcinoma; Adenoma; Administration, Oral; Administration, Rectal; Animals; Bile Acids and Salts; Carcinogens; Carcinoma, Squamous Cell; Cholic Acids; Colon; Colonic Neoplasms; Deoxycholic Acid; Dimethylhydrazines; Feces; Female; Germ-Free Life; Injections, Subcutaneous; Lithocholic Acid; Methylnitrosourea; Mice; Mice, Inbred ICR | 1993 |