Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P08758 (annexin V)
 9,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a new series of Herceptin-platinum(II) binding complexes, Her-nLPt(II) (Her denotes Herceptin; L denotes diamino ligands and L=L1-L4; n=1, 5, or 10). Solution chemistry studies have shown that these complexes are stable under physiological conditions (pH 7.4 in PBS). The platinum(II) compound L1Pt(II)Cl(2) inhibits the growth of a panel of human cancer cell lines at sub-micromolar concentrations. Remarkable cancer-cell-specific cytotoxicity was observed with Her-nL1Pt(II) (n=1, 5, 10) toward Her2/neu-overexpressing cancer cells (SK-BR-3 and SK-OV-3) over normal fibroblast cells. Annexin V apoptosis assays in SK-BR-3 and low-Her2/neu-expressing MCF-7 breast cancer cells further confirmed the critical role of Herceptin with this cancer-cell-specific agent. It was also found that the L1Pt(II)Cl(2) complex is an efficient regulator of the apoptotic genes Bcl-2 in the treated SK-BR-3 cells. Also, enhanced regulatory effects were observed in Her-10L1Pt(II). Taken together, this study suggests a new approach for the development of mAb-platinum(II)-based targeting agents for the treatment of human cancers.
 ...
PMID:Herceptin-platinum(II) binding complexes: novel cancer-cell-specific agents. 1836 39

Enzastaurin (LY317615.HCI), a protein kinase C (PKC)-beta inhibitor, has a radiosensitising effect on 4T1 murine breast cancer and human glioma cells; however, the exact mechanism of this action has not been evaluated. The present study investigated the effects of enzastaurin and gamma irradiation on PKC activity in MCF-7 human breast cancer cells in vitro and in vivo. Enzastaurin (5 microM) in combination with irradiation (2-8 Gy) produced a synergistic decline in MCF-7 clonogenic cell survival. Analysis of MCF-7 cells stained with Annexin V and 7-aminoactinomycin D showed a dose-dependent increase in apoptosis in response to enzastaurin (3, 5 and 7 microM) and irradiation (10 Gy) compared to irradiation alone. This pro-apoptotic effect was confirmed by increases in caspase-3 and -9 activity. In a MCF-7 xenograft model, irradiation with 25 Gy increased PKC-alpha activity by 2.5-fold compared to untreated controls, whereas PKC-epsilon and -betaII activity was increased by 1.8-fold. Radiation-induced activation of all three anti-apoptotic isoforms of PKC was reversed by pre-treatment with enzastaurin (75 mg/kg, twice daily for 3 days). We conclude that enzastaurin has a radiosensitising effect on MCF-7 human xenograft tumours through the reversal of anti-apoptotic activation of PKC isoforms.
 ...
PMID:Enzastaurin renders MCF-7 breast cancer cells sensitive to radiation through reversal of radiation-induced activation of protein kinase C. 1844 27

The methanolic and methane dichloride extracts of aerial parts of Larrea divaricata Cay. (Jarilla) plants exhibited a pronounced cytotoxic effect by arresting cell viability at a level of 35% against the MCF-7 cell line, a human breast adenocarcinoma, while only a weak cytotoxic effect was observed for the aqueous extract. Apoptosis was detected by flow cytometry, using annexin V and by cytological detection with fluorescein diacetate / propidium iodide staining. The annexin V, as well as the uptake of fluorescein diacetate/propidium iodide staining, revealed that methanolic and methane dichloride extracts of L. divaricata treatment of cells resulted in a rapid plasma membrane perturbation and triggered cellular death (>70%). Methanolic extracts were submitted to further treatment by bioassay-guided purification, involving fractionation and chromatography. 0.1% (w/w) nordihydroguaiaretic acid (NDGA) was found, which displayed weak citotoxic activity.
 ...
PMID:Organic extracts of Larrea divaricata Cav. induced apoptosis on tumoral MCF7 cells with an higher cytotoxicity than nordihydroguaiaretic acid or paclitaxel. 1847 37

In the course of searching for novel cytotoxic compounds which can be used in chemotherapy, several Traditional Chinese Medicines (TCM) have been screened by bioassay-guided fractionation and isolation. An extract of rhizomes of Iris tectorum Maxim., a TCM used to treat cancer, exhibited highest potency and led to the isolation of two flavonoids, 7-O-methylaromadendrin and tectorigenin, and four iridal-type triterpenes, iritectols A and B, isoiridogermanal and iridobelamal A. The cytotoxicities of the isolated compounds against four human cancer cell lines were evaluated by the SRB assay. Iritectol B, isoiridogermanal and iridobelamal A showed similar cytotoxicity with IG(50) around 11 microM and 23 microM against MCF-7 and C32 cell lines, respectively. Cell cycle-specific inhibition and apoptosis induced by the isolated compounds were determined using flow cytometry with two sets of co-labelling systems: annexin V-FITC/propidium iodide and fluorescein diacetate/propidium iodide. Iritectol B demonstrated dose-dependent apoptotic effect against COR-L23 cells with an apoptotic rate of 33% at 100 microM. Tectorigenin (an analogue of genistein) showed cell cycle specific inhibition and arrested cells at G(2)/M phase up to 400 microM, but did not demonstrate apoptotic effect against COR-L23 cells up to 1 mM. The overall activities of isolated compounds observed in the present study support the traditional use of Iris tectorum Maxim. in the treatment of cancer.
 ...
PMID:Cytotoxic effects of compounds from Iris tectorum on human cancer cell lines. 1850 14

Overexpression of P-glycoprotein (Pgp) and multidrug resistance protein 1 (MRP1) by tumors results in multidrug resistance (MDR) to structurally unrelated anti-tumor agents. HZ08, a chiral compound, was a newly synthesized tetraisohydroquinoline derivative to reverse Pgp and MRP1 mediated MDR. In present studies, R, S-HZ08 and their racemate reversed the resistance to adriamycin and vincristine of adriamycin-selected human leukemia (K562/ADM) cells that overexpress Pgp. R, S-HZ08 and their racemate modulated adriamycin cytotoxicity when R, S-HZ08 and their racemate were removed 12 h prior to the cytotoxicity assay. In addition, R, S-HZ08 and their racemate increased intracellular accumulation of Rhodamine123 in Caco-2 cells that overexpress Pgp. Furthermore, using a DNA content analysis and an annexin V binding assay, R, S-HZ08 and their racemate effectively reversed the resistance to adriamycin-induced apoptosis in K562/ADM cells. R, S-HZ08 and their racemate also moderately reversed the resistance to adriamycin and vincristine of MCF-7/ADM cells that overexpress MRP1. However, R, S-HZ08 and their racemate hardly affected intracellular glutathione (GSH) levels and glutathione S-transferase (GST) activities in MCF-7/ADM cells. The result showed that R, S-HZ08 and their racemate possibly reverse MDR1 mediated multidrug resistance by a direct interaction with MRP1, not interaction with MRP1 via GSH. Thus, R, S-HZ08 and their racemate should be useful for treating patients with tumors that overexpress both Pgp and MRP1.
 ...
PMID:Reversal of P-glycoprotein and multidrug resistance-associated protein 1 mediated multidrug resistance in cancer cells by HZ08 Isomers, tetrataisohydroquinolin derivatives. 1852 65

N,N-Diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine (DPPE, tesmilifene), a potent chemopotentiating drug currently in Phase III clinical trials of metastatic breast cancer, increases cytotoxicity of anthracyclines and taxanes in a variety of multi-drug resistance expressing (MDR+) tumor cell lines in vitro; inhibits binding of histamine to CYP3A4, a lipid/prostanoid-regulatory P450; and modulates serum levels of HDL/LDL cholesterol and phospholipids in vivo. Since increased exposure of phosphatidylserine (PS) on the outer cell membrane leaflet is associated with apoptosis, increased clearance of dead cells by phagocytes and inhibition of the P-glycoprotein pump, the effect of DPPE on PS synthesis was assessed in vitro in a human breast cancer cell line. MCF-7 cells were incubated with 5 microM DPPE for 24 hr or 5 days, followed by addition of [1-(14)C]arachidonic acid for 4 hr; or [3H]serine for 8 hr. Compared to untreated cells, a 27-42% (p < 0.05) increase in [1-(14)C]arachidonic acid incorporated into all phospholipids, including a 1.9-fold increase (p < 0.05) in PS was observed in DPPE-treated cells. [3H]Serine incorporation into PS was elevated 37%, while the pool size of PS was elevated 23% (p < 0.05) in DPPE-treated cells, indicating elevated de novo PS biosynthesis. Annexin-5 binding studies indicated an elevation in exposure of PS on the surface of the plasma membrane in DPPE-treated cells. DPPE-treatment also resulted in N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine accumulation indicative of phospholipidosis-inducing potential. Thus, the chemopotentiating effect of DPPE may be due to its phospholipidosis-inducing potential and stimulation of PS synthesis leading to an increased exposure of PS on the cell surface which could potentially enhance cancer cell clearance by phagocytes.
 ...
PMID:The phospholipidosis-lnducing potential of the chemopotentiating drug, N,N-Diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine (DPPE, tesmilifene) correlates with its stimulation of phosphatidylserine synthesis and exposure on the plasma membrane in MCF-7 breast cancer cells. 1860 31

Transferrin receptor (TfR) has been used as a target for antibody-based therapy of cancer. Combining anti-TfR antibodies with chemotherapeutic drugs shows potential as one of the strategies for cancer therapy. In this study, we investigated the effects of anti-TfR monoclonal antibody 7579 alone or in combination with chemotherapeutic drugs (5-fluorouracil or doxorubicin) on non-hematopoietic tumor cells (HepG2 and MCF-7) in vitro. We found that 7579 mAb alone could dramatically down-regulate surface TfR expression on tumor cells. Consequently, marked S phase arrest and apoptosis were observed in 7579 mAb-treated tumor cells. In combination with 5-fluorouracil or doxorubicin, 7579 mAb enhanced the growth inhibitory effects of chemotherapeutic drugs on tumor cells. Results of 7AAD/Annexin V staining demonstrated that 7579 mAb enhanced the cytotoxic effects of chemotherapeutic drugs on tumor cells by mainly promoting tumor cell necrosis. Using the median-effect/combination-index isobologram method, we further evaluated the nature of 7579 mAb/chemotherapeutic drug interactions. Synergistic interaction was observed for 7579 mAb combined with 5-fluorouracil whereas additive efficacy was observed for 7579 mAb plus doxorubicin. Our study provided the basis to further develop 7579 mAb-containing chemoimmunotherapy for non-hematopoietic malignancies.
 ...
PMID:An anti-transferrin receptor antibody enhanced the growth inhibitory effects of chemotherapeutic drugs on human non-hematopoietic tumor cells. 1881 95

The active form of vitamin D(3), 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], modulates proliferation and induces differentiation of many cancer cells. A new class of analogs of vitamin D(3) has been synthesized, having two side-chains attached to carbon-20 (Gemini) and deuterium substituted on one side-chain. We have examined six of these analogs for their ability to inhibit growth of myeloid leukemia (HL-60), prostate (LNCaP, PC-3, DU145), lung (H520), colon (HT-29), and breast (MCF-7) cancer cell lines. Dose-response clonogenic studies showed that all six analogs had greater antiproliferative activities against cancer cells than 1,25(OH)(2)D(3). Although they had similar potency, the most active of these analogs was BXL-01-0120. BXL-01-0120 was 529-fold more potent than 1,25(OH)(2)D(3) in causing 50% clonal growth inhibition (ED(50)) of HL-60 cells. Pulse-exposure studies demonstrated that exposure to BXL-01-120 (10(-9)M, 48h) resulted in 85% clonal inhibition of HL-60 growth. BXL-01-0120 (10(-11)M, 4 days) induced the differentiation marker, CD11b. Also, morphologically differentiation was more prominent compared to 1,25(OH)(2)D(3). Annexin V assay showed that BXL-01-0120 (10(-10)M, 4 days) induced significantly (p<0.05) more apoptosis than 1,25(OH)(2)D(3). In summary, these analogs have a unique structure resulting in extremely potent inhibition of clonal proliferation of various types of cancer cells, especially HL-60 cells.
 ...
PMID:Novel Gemini vitamin D(3) analogs have potent antitumor activity. 1893 45

N,N-diethyl-2-[4-(phenylmethyl)phenoxyl]ethanamine (tesmilifene), a tamoxifen derivative with antihistamine activity, greatly enhanced the survival of doxorubicin-treated, advanced stage breast cancer patients in a phase III trial. However, the molecular basis of tesmilifene action is not firmly established. The effects of tesmilifene on activity of several anticancer drugs was investigated using human head and neck squamous cell carcinoma (HNSCC) and breast carcinoma cell lines as a model system. Multidrug resistant (MDR) variants of an HNSCC cell line, HN-5a/V15e, and a breast carcinoma cell line, MCF-7/V25a, both highly overexpressed mdr1 (ABCB1) mRNA and the proteins P-glycoprotein and glutathione transferase-pi. Drug sensitivities were measured by a vital stain after 4 days of continuous exposure to anticancer drug in the absence and presence of tesmilifene at a concentration that alone had no antiproliferative effect. Tesmilifene had minimal effect on drug cytotoxicity against the parental cell lines. However, the same tesmilifene treatment enhanced cytotoxicity of docetaxel, paclitaxel, epirubicin, doxorubicin, and vinorelbine against both MDR cell lines by up to 50%. Flow cytometric measurement of annexin V/propidium iodide staining demonstrated that tesmilifene increased the killing of HN-5a/V15e cells caused by docetaxel after 24 and 48h exposure. Tesmilifene increased accumulation of radiolabelled vincristine in HN-5a/V15e cells, over 4h, by up to 100%. The results suggest that tesmilifene might be effective in the treatment of tumors that are resistant to natural product drugs. The mechanism of enhancement appears to be related to expression of an ABC pump-dependent, MDR phenotype.
 ...
PMID:Enhancement of cytotoxicity of natural product drugs against multidrug resistant variant cell lines of human head and neck squamous cell carcinoma and breast carcinoma by tesmilifene. 1898 63

The mechanism of apoptosis induced by SIRT1 deacetylase inhibitors in both human breast cancer MCF-7 and MCF-7 doxorubicin-resistant cells was studied. MTT assay was used to detect growth-inhibitory effect on the cells. Protein expression was detected by Western blotting. Chromatin condensation was detected by a fluorescent microscope after Hoechst 33342 staining. Cell cycle distribution was analyzed with flow cytometry. Apoptotic cells were detected with Annexin V staining. Nicotinamide (NAM) and Sirtinol, two SIRT1 deacetylase inhibitors, exhibited the similar growth-inhibitory effects on MCF-7/DOX cells and MCF-7 cells, but no potentiation of DOX activities. The arrest at G2/M phase was detected by flow cytometry in both MCF-7 and MCF-7/DOX cells after NAM treatment. Activation of caspase pathway in MCF-7 cells, such as the cleavages of PARP, caspase-6, -7, -9, were observed after exposure to NAM 50 mmol x L(-1), accompanied by the occurrence of chromatin condensation and Annexin V positive cells. However, the cleavages of PARP, caspase-6 and -7 in MCF-7/DOX cells delayed after exposure to NAM for 24 h and obviously increased at 48 h with appearance of chromatin condensation and Annexin V positive cells. SIRT1 deacetylase inhibitors show no cross resistance to MCF-7 drug-resistant cells, and the similar growth-inhibitory actions of them to MCF-7 sensitive and drug-resistant cells by which it is mediated by activation of apoptotic caspase pathway.
 ...
PMID:[Mechanism of apoptosis induced by SIRT1 deacetylase inhibitors in human breast cancer MCF-7 drug-resistant cells]. 1912 63


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