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)

Even if it seems that everything has been said about the influence of estradiol on cell proliferation in human breast cancer cell lines such as MCF-7, T47-D, ZR-75 and MDA-MB-231, in this study of the possible autocrine and/or paracrine role of 17 beta estradiol (E2) on the proliferation of human breast cancer cell lines we nevertheless offer some complementary information in this field of research. We exogenously stimulated the cell lines by the addition to the culture media of E2 and the anti-E2 antibody. The latter neutralizes the effects of any endogenous E2. The cell proliferation was assessed by means of the MTT colorimetric test. We thus showed that the level of sensitivity of various breast cancer cell lines to estradiol in terms of cell proliferation depends on the experimental schedule chosen. Indeed, the addition of E2 to the culture media stimulated the growth of the the ZR-75 and T47-D cell lines conventionally described as estrogen-receptor positive (ER+). For the MCF-7 cell line and the conventionally described as estrogen-receptor negative (ER-) MDA-MB-231 cell line, this is not the case. In sharp contrast, the addition to the culture media of the antibody neutralizing the biophysical activity of E2 sharply decreased the proliferation rate of the four cell lines under study. So these four cell lines in fact seem to be estradiol-sensitive. Thus, those which do not react to the addition of estradiol might use E2 in an autocrine and/or paracrine manner.
 ...
PMID:In vitro estradiol-sensitivity characterization of the MCF-7, ZR-75, MDA-MB-231 and T47-D human breast neoplastic cell lines. 829 58

Conditioned media from 14 short term fibroblast cell lines were mitogenic for human breast cancer cells with different steroid receptor profiles in serum-free culture. Fibroblast-conditioned medium stimulated tritiated thymidine incorporation in short term culture and growth in a longer proliferation study as measured by the MTT colorimetric assay. Conditioned media from benign and malignant epithelial cells were non-stimulatory for breast cancer cells but that derived from endothelial cells showed similar stimulation to fibroblasts. Partial purification of fibroblast-conditioned medium identified a peptide with a molecular weight of approximately 8 kDa that showed no affinity for heparin and was mitogenic for MCF-7 breast cancer cells.
 ...
PMID:Fibroblast stimulation of breast cancer cell growth in a serum-free system. 851 12

The schedule-dependent interaction of paclitaxel and cisplatin was studied in four human carcinoma cell lines: non-small cell lung cancer, A549; breast cancer, MCF7; ovarian cancer, PA1; and colon cancer, WiDr cells. The cells were exposed simultaneously to the drugs for 24 h and sequentially to paclitaxel first for 24 h followed by cisplatin for 24 h, or vice versa, and then incubated in drug-free medium for 4 and 3 days, respectively. Cell growth inhibition was then determined by the 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenyltetrazolium bromide (MTT) reduction assay. The effects of drug combinations at the IC80 level were analyzed by the isobologram method. On simultaneous exposure to paclitaxel and cisplatin, additive and subadditive (slight antagonistic) effects were observed in A549, MCF7, and PA1 cells, while sub-additive and protective (antagonistic) effects were observed in WiDr cells. On sequential exposure to paclitaxel first, followed by cisplatin, additive effects were observed in all cell lines. On sequential exposure to cisplatin first, followed by paclitaxel, additive effects were observed in PA1 cells, while additive, sub-additive, and protective effects were observed in A549, MCF7, and WiDr cells. These findings suggest that the interaction of paclitaxel and cisplatin is schedule- and cell line-dependent. The optimal schedule of this combination may be paclitaxel first followed by cisplatin.
 ...
PMID:In vitro schedule-dependent interaction between paclitaxel and cisplatin in human carcinoma cell lines. 861 5

The effect of ursolic acid on the proliferation of MCF-7 human breast tumor cells was studied. During investigations of the anti-proliferative effects of this triterpene, we observed a clear difference between MTT colorimetric assay and direct cell counting, particularly 24 h after drug treatment. The MTT assay showed a stimulation of formazan production in the first 24 h exposure of cells to drug. The maximum stimulation was obtained with 15 and 20 microM of ursolic acid (about 30 - 40% of increase with respect to control); however, the number of cells was not increased as revealed by direct cell counting. Ursolic acid is a potent inhibitor of MCF-7 cell proliferation. This triterpene exhibits both cytostatic and cytotoxic activity. It exerts an early cytostatic effect at G1 followed by cell death. Cell cycle analysis is performed by propidium iodide staining and flow cytometry technique. These results suggest that alterations in cell cycle phase redistribution of MCF-7 human breast cancer, by ursolic acid, may significantly influence MTT reduction to formazan.
 ...
PMID:MCF-7 cell cycle arrested at G1 through ursolic acid, and increased reduction of tetrazolium salts. 861 58

The schedule-dependent interaction of paclitaxel and doxorubicin was evaluated in four human cancer cell lines. The cells were exposed simultaneously or sequentially to the two agents for 24 h, and were then incubated in drug-free medium for 4 and 3 days, respectively. The cell growth inhibitions were determined by the MTT assay. The cytotoxic interactions at the IC80 level were evaluated by the isobologram method of Steel and Peckham. In non-small cell lung cancer A549, breast cancer MCF7 and colon cancer WiDr cells, antagonistic effects were observed for the paclitaxel and doxorubicin combination on simultaneous exposure to the two agents and on sequential exposure to doxorubicin followed by paclitaxel, while additive effects were observed for the combination on sequential exposure to paclitaxel followed by doxorubicin. In ovarian cancer PA1 cells, additive effects were observed for all schedules. These findings suggest that sequential administration of paclitaxel followed by doxorubicin may be the most suitable sequence, while the simultaneous administration of the two agents and the sequential administration of doxorubicin followed by paclitaxel may result in less tumour cell kill than anticipated. Further preclinical and clinical studies are required to elucidate the relationship between paclitaxel and doxorubicin with regard to both antitumour activity and toxicity.
 ...
PMID:Schedule-dependent interaction between paclitaxel and doxorubicin in human cancer cell lines in vitro. 865 67

The reversing effect of p-glycoprotein (Pgp) inhibitors on the multidrug resistance (MDR) phenotype is well established in a variety of MDR cell lines. The interactions of these inhibitors with individual MDR drugs in the respective parental lines, however, is less documented. This kind of information is not only essential for understanding of the outcome of clinical trials for MDR modulation in heterogeneous tumor populations but also important for evaluating of new Pgp blockers. Interaction of the Pgp inhibitor, thaliblastine (TBL), with several MDR drugs was therefore investigated in sensitive human breast cancer cell line (MCF-7) as well as adriamycin (AdR) selected MDR subline MCF/AdR. While the resistance to anthrapyrazole CI941 was completely overcome by simultaneous exposure to TBL (8 microM) in a 48 h exposure MTT assay compared with MCF-7 cells exposed to the same combination, only partial reversal was achieved in the case of AdR and etoposide (VP-16), but 240-fold hypersensitivity (or collateral sensitivity) was obtained in the MCF/AdR cells treated with taxol plus TBL, with IC50s of 0.10 +/- 0.03 microM and 24.6 +/- 5.0 microM in the resistant and sensitive cell lines, respectively. In the parental MCF-7 cells, on the other hand, no change of AdR cytotoxicity by simultaneous exposure to TBL was observed. There was an enhancement of CI941 cytotoxicity but an antagonism against taxol and VP-16 obtained upon addition of TBL to the treatment with the drugs in the MCF-7 parental cell line. Our results demonstrate that while TBL can overcome the resistance to each of the MDR drugs studied in MCF/AdR cells, albeit to a different extent varying from the partial reversal to the hypersensitivity, TBL co-exposure does not uniformly increase the cytotoxicity of these drugs in the parental MCF-7 cells.
 ...
PMID:Differential interactions of Pgp inhibitor thaliblastine with adriamycin, etoposide, taxol and anthrapyrazole CI941 in sensitive and multidrug-resistant human MCF-7 breast cancer cells. 904 12

Inositol hexaphosphate (InsP6 or IP6) is an active ingredient of high fiber diet that has anti-cancer action in both in vitro and in vivo models. Recently we have demonstrated that InsP6 significantly inhibits DMBA-induced rat mammary cancer in vivo. To test the hypothesis that InsP6 mediates its function via inhibition of cell proliferation irrespective of hormonal dependence, its effect on growth inhibition and differentiation were studied in two human mammary carcinoma cell lines with different estrogen receptor status. Cell growth was measured by MTT incorporation assay, DNA synthesis by 3H-Tdr uptake and differentiation marker lactalbumin by immunocytochemistry. Dose-dependent growth inhibition was observed in both estrogen receptor-positive (MCF-7) and receptor-negative cells (MDA-MB-231). Statistically significant growth inhibition (p < 0.05) was observed starting at 1 mM InsP6 as early as after the first day of treatment and continued up to 6 days for both the cell lines. DNA synthesis in both the cell lines was suppressed by InsP6 occurring as early as 3 h after the beginning of treatment and continued up to 48 h; significant inhibition (p < 0.05) started at 1 mM InsP6 after 6 h of treatment. Compared to untreated cells, a 5-fold (p < 0.05) and 22-fold (p < 0.01) increase in expression of lactalbumin, associated with luminal cell differentiation was identified by immunocytochemistry after 48 h of treatment with 1 and 5 mM InsP6. Our data show that the inhibition of DNA synthesis and cell growth and induction of differentiation of human mammary cancer cell lines by InsP6 is independent of the estrogen receptor status of the cells. Taken together with results from in vivo studies, InsP6 may be an important candidate for the prevention and treatment of human breast cancer.
 ...
PMID:Novel anti-cancer functions of IP6: growth inhibition and differentiation of human mammary cancer cell lines in vitro. 904 2

The pathogenesis of tumor-induced osteolysis (TIO) following breast cancer metastases in bone remains unclear. We postulated that osteoblasts could be target cells for the secretory products of breast cancer cells. We previously showed that serum-free conditioned medium (CM) of the breast cancer cell line MCF-7 inhibits DNA synthesis by 75% of control values in osteoblast-like cells SaOS-2 and that this effect is only in a minor part due to transforming growth factor beta secretion. To establish the specificity of our observations and to look for other biologically active factors, we have tested the effects of medium conditioned by several cancer and noncancer cell lines (breast, colon, placenta, or fibrosarcoma) on the proliferation of osteoblast-like cells (SaOS-2, MG-63), normal human osteoblasts, human fibrosarcoma cells, and normal human fibroblasts. Culture medium (1:2) of the breast cancer cell lines MCF-7, T-47D, MDA-MB-231, and SK-BR-3 inhibited by 25-50% the proliferation of osteoblast-like cells SaOS-2, MG-63, and normal osteoblasts as evaluated by the MTT survival test or [3H]thymidine incorporation. MCF-7 cells completely inhibited the proliferation of normal human osteoblasts in coculture. This inhibitory effect was reversible and not due to cytotoxicity. Moreover, the cyclic adenosine monophosphate (cAMP) response to parathyroid hormone (PTH) of osteoblast-like cells SaOS-2 was also increased by 100-240% by the same CM. Such activities were, however, not detected in medium from the breast noncancer cell line HBL-100 or in the medium conditioned by non-breast cancer cell lines (COLO 320DM, HT-29, JAR, or HT-1080). Medium from the breast cancer cells had no effect on normal human fibroblasts or fibrosarcoma cells (HT-1080), suggesting the specificity of their action on human osteoblasts. After partial purification by ultrafiltration and size-exclusion chromatography, we found that medium of T-47D cells contained at least three nonprostanoid factors of low molecular weights (apparent MW of 700, 1500, and 4000 D) which affected human osteoblast-like cells. These factors were heat stable and could be peptides without disulfide bonds. In summary, our data show that human breast cancer cells release soluble factors that inhibit osteoblast proliferation and increase their cAMP response to PTH, indicating that osteoblasts could be important target cells for breast cancer cells and could be involved in the process of TIO.
 ...
PMID:Secretory products of breast cancer cells specifically affect human osteoblastic cells: partial characterization of active factors. 910 66

HER-2/neu overexpression has been associated with poor prognosis in human breast cancer. Many of these cancers are also ER-positive. A logical therapeutic approach for patients who are ER-positive and overexpress HER-2/neu may be to block both the ER and the HER-2/neu pathways. In our study, we used both the MTT tetrazolium dye assay and 3H-thymidine incorporation to measure the effects of the anti-estrogen Tamoxifen or the 4D5 anti-HER-2/neu antibody alone or in combination on the growth of BT474 human breast cancer cells which express ER and overexpress HER-2/neu. We found an enhanced inhibitory effect on cell proliferation with the combination of Tamoxifen and the antibody compared to that seen by either agent alone. This simultaneous interruption of both the ER and the HER-2/neu pathways may be relevant in the clinical treatment of patients who are both ER-positive and overexpress HER-2/neu.
Breast Cancer Res Treat 1997 Jan
PMID:Enhanced anti-proliferative activity of the combination of tamoxifen plus HER-2-neu antibody. 911 13

Recent studies have demonstrated that following estrogen ablation, estrogen responsive breast cancer cells undergo apoptosis. In addition, estrogen receptor (ER) expression has been strongly correlated with the expression of the bcl-2 gene product, p26Bcl-2 protein, which is known to inhibit apoptosis. In the present studies, we investigated whether estrogen affects the intracellular levels of p26Bcl-2 and thereby modulates taxol-induced apoptosis of estrogen responsive human breast cancer MCF-7 cells. Transfer of MCF-7 cells to a culture-medium without estrogens reduced their intracellular p26Bcl-2 levels by 50%. Inclusion of 0.1 microM estradiol in the medium produced approximately a four-fold increase in p26Bcl-2, but not p29Bcl-x1, or p21Bax levels; the expression of the c-myc and mdr-1 genes remained unchanged. Estradiol-induced four-fold increase in the ratio of the p26Bcl-2 to p21Bax levels caused a significant decline in the lethal, kilobase size DNA fragments of apoptosis, which had resulted when MCF-7 cells were cultured in a medium without estrogen. In addition, in MCF-7 cells, estradiol-induced increase in the intracellular p26Bcl-2 to p21Bax ratios was associated with a significant reduction in the large-sized DNA fragmentation induced by treatment with taxol. The increased ratios also protected MCF-7 cells against taxol-mediated cytotoxicity as assessed by the MTT assay. These results suggest that by modulating p26Bcl-2 levels, estrogens may affect the antitumor activity of taxol and potentially of other anti-breast cancer drugs against estrogen responsive human breast cancer cells.
Breast Cancer Res Treat 1997 Jan
PMID:Estrogen increases intracellular p26Bcl-2 to p21Bax ratios and inhibits taxol-induced apoptosis of human breast cancer MCF-7 cells. 911 21


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