Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anthracyclines and docetaxel are frequently used agents in the chemotherapy of breast cancer. In this study we examined the role of inducible nitric oxide synthase (iNOS) expression during the cytotoxicity of these drugs in the MCF-7 breast cancer cell line. Cell viability and cytotoxicity were evaluated by the trypan blue dye exclusion method. Apoptosis and necrosis were determined by the acridine orange/ethidium bromide dye method. The percentage of apoptotic cells was significantly higher with doxorubicin. However, total cytotoxic cell numbers were higher in the docetaxel group compared with doxorubicin, with respect to the control. Most of the cells were seen to be necrotic with the dye method. Cell extracts during the apoptotic process were applied to immunoblot by anti-iNOS monoclonal antibodies. While there was an increase in iNOS expression during docetaxel induced-cytotoxicity, a significant decrease in iNOS expression was detected during doxorubicin-induced cytotoxicity. The Griess method was used for detection of nitrate levels. It was compatible with immunoblot results. These data open a window for further studies to understand the mechanism underlining the cytotoxicity of docetaxel and doxorubicin.
 ...
PMID:Differential effects of doxorubicin and docetaxel on nitric oxide production and inducible nitric oxide synthase expression in MCF-7 human breast cancer cells. 1530 29

Antioxidants play an important role in inhibiting and scavenging radicals, thus providing protection to humans against infections and degenerative diseases. Literature shows that the antioxidant activity is high on herbal and vegetable plants. Realizing the fact, this research was carried out to determine total antioxidant activity and the potential anticancer properties in three types of selected local vegetable shoots such as Diplazium esculentum (paku shoot), Manihot utillissima (tapioca shoot) and Sauropous androgynus (cekur manis). The research was also done to determine the effect of boiling, on total antioxidant activity whereby samples of fresh shoots are compared with samples of boiled shoots. In every case, antioxidant activity is compared to alpha-tocopherol and two methods of extraction used are the organic and the aqueous methods. Besides that, two research methods used were the ferric thiocyanate (FTC) and thiobarbituric acid (TBA) with absorbance of 500nm and 532nm respectively. Oneway ANOVA test at P<0.05 determines significant differences between various samples. In the cytotoxic study, the ethanolic extract and several cell lines i.e. breast cancer (MDA-MB-231 and MCF-7), colon cancer (Caco-2), liver cancer (HepG2) and normal liver (Chang liver) were used. The IC(50)-value was determined by using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay. The antioxidant study found that all the samples in both aqueous and organic extraction were significantly different. The total antioxidant activity values of aqueous extract in descending order are as follows: M. utilissima (fresh) >D. esculentum (fresh) >S.androgynus (fresh) > M.utilissima (boiled) > D. esculentum (boiled) > S.androgynus (boiled). It also was found that S.androgynus shoots ethanolic extract was able to inhibit the viability of the breast cancer cell lines, MDA-MB-231 with the IC50 value of 53.33 micrograms/ml. However, S.androgynus shoots and D. esculentum shoots ethanolic extracts did not inhibit the viability of MDA-MB-231 cell line. While, the tapioca shoot ethanolic extract was able to inhibit the viability of MCF-7 cell line with the IC(50) value of 52.49 micrograms/ml. S.androgynus shoots and D.esculentum shoots ethanolic extracts did not give an IC(50) value against the MCF-7 cell line. S.androgynus, tapioca and D.esculentum shoots ethanolic extracts did not show cytotoxic effect against the Caco-2 and HepG2. There was no IC(50)-value from any sample against Chang Liver cell line. In conclusion, the antioxidant activity of both fresh and boiled samples were higher than alpha-tocopherol, although fresh vegetable shoots were found to be higher in antioxidant activity compared to boiled shoots. This study also suggested that S.androgynus shoots and tapioca shoots have potential as an anticancer agent against certain breast tumours.
 ...
PMID:Determination of total antioxidant activity in three types of local vegetables shoots and the cytotoxic effect of their ethanolic extracts against different cancer cell lines. 1533 45

The objective of this study was to determine the anti cancer effects of red spinach (Amaranthus gangeticus Linn) in vitro and in vivo. For in vitro study, microtitration cytotoxic assay was done using 3-(4,5-dimethylthiazol-2-il)-2,5-diphenil tetrazolium bromide (MTT) kit assay. Results showed that aqueous extract of A gangeticus inhibited the proliferation of liver cancer cell line (HepG2) and breast cancer cell line (MCF-7). The IC(50) values were 93.8 mu g/ml and 98.8 mu g/ml for HepG2 and MCF-7, respectively. The inhibitory effect was also observed in colon cancer cell line (Caco-2), but a lower percentage compared to HepG2 and MCF-7. For normal cell line (Chang Liver), there was no inhibitory effect. In the in vivo study, hepatocarcinogenesis was monitored in rats according to Solt and Farber (1976) without partial hepatectomy. Assay of tumour marker enzymes such as glutathione S-transferase (GST), gamma-glutamyl transpeptidase (GGT), uridyl diphosphoglucuronyl transferase (UDPGT) and alkaline phosphatase (ALP) were carried out to determine the severity of hepatocarcinogenesis. The result found that supplementation of 5%, 7.5% and 10% of A. gangeticus aqueous extract to normal rats did not show any significant difference towards normal control (P <0.05). The exposure of the rats to chemical carcinogens diethylnitrosamine (DEN) and 2-acetylaminofluorene (AAF) showed a significant increase in specific enzyme activity of GGT, GST, UDPGT and ALP compared to normal control (P <0.05). However, it was found that the supplementation of A. gangeticus aqueous extract in 5%, 7.5% and 10% to cancer-induced rats could inhibit the activity of all tumour marker enzymes especially at 10% (P <0.05). Supplementation of anti cancer drug glycyrrhizin at suggested dose (0.005%) did not show any suppressive effect towards cancer control (P <0.05). In conclusion, A. gangeticus showed anticancer potential in in vitro and in vivo studies.
 ...
PMID:Potential anticancer effect of red spinach (Amaranthus gangeticus) extract. 1556 47

New bisoxynaphthalimidopolyamines (BNIPOPut, BNIPOSpd and BNIPOSpm) were synthesized. Their cytotoxic properties were evaluated against breast cancer MCF 7 cells and compared with bisnaphthalimidopolyamines BNIPSpd and BNIPSpm. Among the bisoxynaphthalimido polyamines, BNIPOSpm and BNIPOSpd exhibited cytotoxic activity with an IC50 f 29.55 and 27.22 microM, respectively, while BNIPOPut failed to exert significant cytotoxicity after 48-h drug exposure. DNA binding was determined by midpoint of thermal denaturation (Tm) measurement, ethidium bromide displacement and DNA gel mobility. Both BNIPOSpm and BNIPOSpd exhibited strong binding affinities with DNA. BNIPOPut had the least effect. The results were compared with other cytotoxic bisnaphthalimido compounds (BNIPSpm and BNIPSpd) previously reported by us. Using the single cell gel electrophoresis assay, it was found that BNIPSpm and BNIPSpd caused substantial DNA damage to MCF 7 treated cells while BNIPOSpm showed no significant effect over a range of drug concentrations after 4-h drug exposure. However, after 12-h drug exposure, BNIPOSpm had induced significant DNA damage similar to that of BNIPSpm (after 4-h drug exposure). Fluorescence microscopic analysis revealed that at 1 microM drug concentration and after 6-h drug exposure, both BNIPSpm and BNIPSpd were located within the cell while the presence of BNIPOSpm, was not observed. Therefore, we conclude that BNIPSpd, BNIPSpm and BNIPOSpm induce DNA damage consistent with their rate of uptake into the cells.
 ...
PMID:Synthesis and biological activities of bisnaphthalimido polyamines derivatives: cytotoxicity, DNA binding, DNA damage and drug localization in breast cancer MCF 7 cells. 1558 10

Membrane proteins play a central role in the interaction of the cell with its environment and in the function of subcellular organelles. The current study focused on developing a better understanding of the membrane proteome of two well-characterized breast cancer cell lines. Membranes from osmotically lysed BT474 and MCF7 cells were treated with cyanogen bromide followed by a combination of trypsin and Staphylococcus V8 protease to obtain hydrophilic peptides from membrane proteins. The complex peptide mixtures obtained were separated by 2-dimensional liquid chromatography coupled online with a nano-electrospray ionization ion trap mass spectrometer (2D LC/nanoESI-MS). The strong cation exchange column used in the first dimension of the separation was eluted in an automated fashion using a series of salt steps of increasing concentration. Peptides eluted from each of the salt steps were separated using a capillary reversed-phase HPLC column, the output of which was directed through a nano-electrospray fused silica tip into the mass spectrometer. Peptides were fragmented by collision-induced dissociation (CID) and analyzed by data-dependent MS/MS followed by database searching using the Sequest algorithm. Analysis of the data revealed both similarities and expected differences between proteins identified from these cell lines. As demonstrated by others, mRNA and the HER2/neu protein tyrosine kinase-linked receptor in BT474 cells is up regulated compared to its level in MCF7, while the expression of the estrogen receptor alpha is known to be up regulated in MCF7 cells. As expected, our studies showed identification of peptides from HER2 in BT474 while estrogen receptor peptides were detected in the MCF7 line. A total of 604 proteins were identified from BT474 membranes while 313 proteins were found from MCF7. The results are discussed in terms of the known differences in both protein and mRNA expression between these two breast cancer cell lines and also in the context of other known phenotypic differences between these cells.
 ...
PMID:2D LC/MS analysis of membrane proteins from breast cancer cell lines MCF7 and BT474. 1559 38

Anthocyanidins, the aglycones of anthocyanins, impart brilliant colors in many fruits and vegetables. The widespread consumption of diets rich in anthocyanin and anthocyanidins prompted us to determine their inhibitory effects on human cancer cell proliferation. Five anthocyanidins, cyanidin (1), delphinidin (2), pelargonidin (3), petunidin (4) and malvidin (5), and four anthocyanins, cyanidin-3-glucoside, cyanidin-3-galactoside, delphinidin-3-galactoside and pelargonidin-3-galactoside were tested for cell proliferation inhibitory activity against human cancer cell lines, AGS (stomach), HCT-116 (colon), MCF-7 (breast), NCI H460 (lung), and SF-268 (Central Nervous System, CNS) at 12.5-200 microg/mL concentrations. The viability of cells after exposure to anthocyanins and anthocyanidins was determined by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) colorimetric methods. The anthocyanins assayed did not inhibit cell proliferation of cell lines tested at 200 microg/mL. However, anthocyanidins showed cell proliferation inhibitory activity. Malvidin inhibited AGS, HCT-116, NCI-H460, MCF-7 and SF-268 cell growth by 69, 75.7, 67.7, 74.7 and 40.5%, respectively, at 200 microg/mL. Similarly, pelargonidin inhibited AGS, HCT-116, NCI H460, MCF-7 and SF-268 cell growth by 64, 63, 62, 63 and 34%, respectively, at 200 microg/mL. At 200 microg/mL, cyanidin, delphinidin and petunidin inhibited the breast cancer cell growth by 47, 66 and 53%, respectively. This is the first report of tumor cell proliferation inhibitory activity by anthocyanidins.
 ...
PMID:Human tumor cell growth inhibition by nontoxic anthocyanidins, the pigments in fruits and vegetables. 1568 Mar 11

Doxorubicin (Adriamycin) is the most active drug in the treatment of breast cancer. The aim of this study was to investigate the interaction of doxorubicin and retinoids in the inhibition of proliferation of hormone sensitive (ER+) human breast cancer cell line MCF-7 and to find out whether this combination can result in the enhancement of its therapeutic effect. As a comparison we also used estradiol and tamoxifen. We also made an attempt to elucidate the effect of these compounds on the stimulation of the apoptotic pathway in breast cancer cells. Cell proliferation in a 24-hour culture was assessed by [3H] thymidine incorporation into cancer cells and by immunocytochemical analysis of cellular cycle-related PCNA and Ki-67 antigens expression, after the incubation of the cell culture with 10, 20 and 50 nM doxorubicin (DOX), 2 nM estradiol (E2), 10 microM tamoxifen (TAM) and 1 nM, 0.01, 0.1, 1 and 10 microM of all-trans retinoid acid (ATRA). The assessment of cell viability and analysis of apoptotic and necrotic cells were performed after the 72-hour incubation of the culture with the examined substances and following apoptosis induction using acridine orange and ethidine bromide. Of the doxorubicin concentrations used in the study, 20 nM inhibited thymidine incorporation to 84.83 +/- 10.00% (control=100%). In the same culture conditions, 2 nM E2 stimulated cancer cells to 157.09 +/- 8.84%. Concentrations of 10 microM TAM and 10 microM ATRA inhibited the proliferation to 63.16 +/- 7.85% and 52.19 +/- 3.21%, respectively. A statistically significant reduction of these values was observed when 20 nM DOX was added to medium with E2 - 39.24 +/- 7.6%, TAM - 48.34 +/- 2.05% and ATRA - 21.98 +/- 1.69%, respectively; the percentage of PCNA- and Ki-67-positive cells was also reduced. Despite high antiproliferative efficacy of 20 nM DOX and 10 microM ATRA combination, the percentage of apoptotic cells was only 25 +/- 0.81%, being similar to that obtained in the culture with 20 nM DOX. The concentrations of 10, 20 and 50 nM DOX that were used to inhibit the proliferation of MCF-7 cell line were not particulary effective. The inhibitory effect was obtained when 20 nM of DOX and E2, TAM or ATRA were used simultaneously. The use of E2 caused a two-fold decrease in the percentage of proliferating cells. It was also shown that the effectiveness of DOX in combination with ATRA is significantly higher than that of DOX combined with TAM, which might suggest a valuable approach to the treatment of breast cancer.
 ...
PMID:The effect of doxorubicin and retinoids on proliferation, necrosis and apoptosis in MCF-7 breast cancer cells. 1570 48

Chitosans are linear polysaccharides of natural origin that show potential as carriers in drug and gene delivery. Introducing quaternisation on the chitosan backbone renders the polymer soluble over a wider pH range and confers controlled cationic character. This study aims to investigate the effect of increasing quaternisation and therefore, positive charge on cell viability and transfection. Oligomeric and polymeric chitosans were trimethylated, the toxicity and transfection efficiency of these derivatives were tested with respect to increasing degree of trimethylation. The cytoxicity of polymer and oligomer derivatives alone and of their complexes with plasmid DNA were determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay on COS-7 (monkey kidney fibroblasts) and MCF-7 (epithelial breast cancer) cells. Transfection efficiency was investigated using the pGL3 luciferase reporter gene on the same cell lines. Complexes were characterised for their stability by gel electrophoresis. Cytotoxicity results showed that all derivatives were significantly less toxic than linear polyethylenimine (PEI). A general trend of increasing toxicity with increasing degree of trimethylation was seen. However, higher toxicity was seen in polymeric chitosan derivatives over oligomeric chitosan derivatives at similar degrees of trimethylation. All derivatives complexed pGL3 luc plasmid DNA efficiently at 10:1 ratio and three (TMO44, TMC57 and TMC93) were able to transfect MCF-7 cells with greater efficiency than PEI; 16, 23 and 50-fold, respectively. TMC57, TMC93 and all TMOs gave appreciable transfection of COS-7 cells.
 ...
PMID:Trimethylated chitosans as non-viral gene delivery vectors: cytotoxicity and transfection efficiency. 1582 Apr 11

The p53R2 gene encodes the ribonucleotide reductase (RR) small subunit 2 homologue, and is induced by several stress signals activating p53, such as DNA-damaging agents. The p53R2 gene product causes an increase in the deoxynucleotide triphosphate (dNTP) pool in the nucleus, which facilitates DNA repair and synthesis. We hypothesized that p53R2 would be a good molecular target for cancer gene therapy. In this study, three human oral cancer cell lines (SAS, HSC-4 and Ca9-22), a human breast cancer cell line MCF-7, and a normal human fibroblast cell line NHDF were tested. We silenced the expression of p53R2 with the highly specific post-transcriptional suppression of RNA interference (RNAi). We investigated p53R2 expression with the reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. The sensitivity to anticancer agents was evaluated by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The expression of p53R2 showed no association with the mutational status of p53. The cancer cell lines with higher p53R2 expression were more resistant to 5-FU. RNAi-mediated p53R2 reduction selectivity inhibited growth and enhanced chemosensitivity in cancer cell lines but not in normal fibroblasts. These results suggest that basal transcription of p53R2 could be associated with the sensitivity to anticancer agents. Moreover, we assessed the possibility that p53R2 would be a good molecular target, and report that RNAi targeting of p53R2 could be useful for oral cancer gene therapy.
 ...
PMID:Silencing of the p53R2 gene by RNA interference inhibits growth and enhances 5-fluorouracil sensitivity of oral cancer cells. 1589 Feb 38

We previously reported that 17-beta-estradiol (E2)-induced mitochondrial reactive oxygen species (mtROS) act as signaling molecules. The purpose of this study was to investigate the effects of E2-induced mtROS on cell cycle progression. E2-induced cell growth was reduced by antioxidants N-acetyl-L-cysteine (NAC), catalase, and the glutathione peroxidase mimic ebselen. Flow cytometry showed that mitochondrial blockers of protein synthesis (chloramphenicol), transcription and replication (ethidium bromide), and function (rotenone, rhodamine 6G) blocked E2-induced G1 to S transition. Reduction of E2-induced DNA synthesis in the presence of mitochondrial blockers occurred without influencing the level of ATP. Additionally, the mitochondrial blockers inhibited the E2-induced expression of early cell cycle genes such as cyclins D1, D3, E1, E2, and B2. NAC or rotenone reduced E2-induced cyclin D1 expression. Furthermore, E2-induced binding of AP-1 and CREB to the TRE and CRE response sequences, respectively, in the promoter of cyclin D1 was inhibited by NAC or rotenone. In addition, E2-induced expression of PCNA, PRC1, and bcl-2 were inhibited by mitochondrial blockers. These data indicate that E2-induced mtROS are involved in the regulation of early G1-phase progression. Since neither antioxidants nor mitochondrial blockers used in this study are reported to bind the estrogen receptor (ER), our findings suggest that E2-induced mtROS modulates G1 to S transition and some of the early G1 genes through a nongenomic, ER-independent signaling pathway. Thus, our results suggest (1) a new paradigm that estrogen-induced mitochondrial oxidants control the early stage of cell cycle progression and (2) provide the basis for the discovery of novel antioxidant-based drugs or antioxidant gene therapies for the prevention and treatment of estrogen-dependent breast cancer.
 ...
PMID:Estrogen-induced G1/S transition of G0-arrested estrogen-dependent breast cancer cells is regulated by mitochondrial oxidant signaling. 1589 99


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>