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Query: UMLS:C0276241 (MCF)
 28,353 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Estrogen receptor (ER)-positive breast cancers initially respond well to estrogen ablation treatment but finally acquire refractoriness, the phenomenon that is a major clinical problem. Because some breast cancers synthesize estradiol (E(2)) and E(2) synthesis is regulated by gonadotropins in normal ovaries, and because circulating gonadotropins are elevated in postmenopausal women and during estrogen ablation treatment, we hypothesized that gonadotropins might modulate estrogen synthesis/metabolism in breast cancer tissue as well. To test this possibility, MCF-7 cells were treated with dehydroepiandrosterone (DHEA) or human chorionic gonadotropin (hCG; approximately LH), each alone or in combination. Cell growth (3-day treatment) was assayed by the MTT method and estrogen synthesis (24-hour treatment) was measured using the ERE-luciferase reporter system. First, MCF-7 cell growth was stimulated by DHEA in a concentration-dependent manner with a maximal effect at 10(-4) M. Although hCG alone did not have a significant proliferative effect, hCG significantly and dose dependently stimulated MCF-7 cell growth in the presence of a submaximal concentration of DHEA (10(-7 )M). This stimulatory effect of DHEA and hCG was blocked by a pure antiestrogen ICI182,780 and an aromatase inhibitor, arimidex. Using MCF-7 cells transfected with the ERE-luciferase reporter system, hCG treatment was shown to increase ERE-mediated transcription. These results indicate that MCF-7 cells intrinsically converted DHEA into E(2) upon hCG stimulation, then grew their own cells DHEA- and hCG-dependently. We conclude that gonadotropins can act on breast cancer cells and accelerate conversion of DHEA into estrogens, thereby stimulating growth of estrogen-dependent tumor cells. This phenomenon, at least in part, could explain: (1) an increased tissue concentration of E(2) in postmenopausal breast cancer; (2) acquisition of hormone refractoriness during estrogen ablation treatment, and (3) the effectiveness of GnRH antagonist/superagonist in some postmenopausal breast cancer patients.
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PMID:Gonadotropins stimulate growth of MCF-7 human breast cancer cells by promoting intracellular conversion of adrenal androgens to estrogens. 1109 52

Multidrug resistance mediated by overexpression of P-glycoprotein (P-gp) is a major obstacle in the chemotherapeutic management of cancer. The objectives of the current work were to examine if fatty acids affect the intracellular transport and dynamics of doxorubicin in drug-resistant cancer cell lines, and to assess if such effects were mediated through modulation of P-gp efflux pump activity. Among the range of fatty acids tested in this study, eicosapentaenoic acid diester (EPADI) increased doxorubicin accumulation [A] to 137% and retention [R] to 212% in doxorubicin-resistant MCF-7/ADR breast carcinoma cells, and [A] to 147% and [R] to 163% in vinblastine-resistant KBVI nasopharyngeal carcinoma cells. Consistent with EPADI-induced increases in intracellular doxorubicin concentrations, EPADI (10 microg/ml) sensitized MCF-7/ADR cells to the cytotoxic effects of doxorubicin (1 microg/ml) as assessed by MTT assay (viability < 50% of control), while EPADI itself displayed no cytotoxicity. The combination of EPADI (10 microg/ml) with verapamil (1 microM) resulted in a considerable increase in the [A] and [R] of the model P-gp substrate rhodamine-123 within drug-resistant cells compared to when either agent were used alone. KBV1 cells treated with combination of EPADI (10 microg/ml) and verapamil (1 microM) achieved 160% and 1120% greater [A] and [R] of rhodamine-123, respectively, compared to untreated cells. The P-gp modulatory effects of EPADI either alone, or as part of a combination with more potent inhibitors, should be further investigated.
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PMID:The effect of fatty acids and analogues upon intracellular levels of doxorubicin in cells displaying P-glycoprotein mediated multidrug resistance. 1114 35

It has been suggested that dietary interventions may improve the effectiveness of cancer chemotherapy. We have examined the combined in vitro cytotoxicity of paclitaxel and the fatty acids gamma-linolenic acid (GLA, 18:3n-6) and oleic acid (OA, 18:1n-9) in human breast carcinoma MDA-MB-231 cells. The effect of fatty acids on paclitaxel chemosensitivity was determined by comparing IC(50) and IC(70) (50 and 70% inhibitory concentrations, respectively) obtained when the cells were exposed to IC(50) and IC(70) levels of paclitaxel alone and fatty acids were supplemented either before or during the exposure to paclitaxel. The 3-4,5-dimethylthiazol-2-yl-2,5-diphenyl-tetrazolium bromide (MTT) assay was used to determine cell growth inhibition. GLA by itself showed antiproliferative effects, and a possible GLA-paclitaxel interaction at the cellular level was assessed by the isobologram and the combination-index (CI) methods. Isobole analysis at the isoeffect levels of 50 and 70% revealed that drug interaction was predominantly synergistic when GLA and paclitaxel were added concurrently for 24 h to the cell cultures. Interaction assessment using the median-effect principle and the combination-index (CI) method showed that exposure of MDA-MB-231 cells to an equimolar combination of concurrent GLA plus paclitaxel for 24 h resulted in a moderate synergism at all effect levels, consistent with the results of the isobologram analysis. When exposure to GLA (24 h) was followed sequentially by paclitaxel (24 h) only an additive effect was observed. The GLA-mediated increase in paclitaxel chemosensitivity was only partially abolished by Vitamin E, a lipid peroxidation inhibitor, suggesting a limited influence of the oxidative status of GLA in achieving potentiation of paclitaxel toxicity. When OA (a non-peroxidisable fatty acid) was combined with paclitaxel, an enhancement of chemosensitivity was found when OA was used concurrently with paclitaxel, although less markedly than with GLA. Pretreatment of MDA-MB-231 cells with OA for 24 h prior to a 24 h paclitaxel exposure produced greater enhancement of paclitaxel sensitivity at high OA concentrations than the concurrent exposure to OA and paclitaxel. The OA-induced sensitisation to paclitaxel was not due to the cytoxicity of the fatty acid itself. When these observations were extended to three additional breast carcinoma cell lines (SK-Br3, T47D and MCF-7), simultaneous exposure to GLA and paclitaxel also resulted in synergism. GLA preincubation followed by paclitaxel resulted in additivity for all cell lines. Simultaneous exposure to paclitaxel and OA enhanced paclitaxel cytotoxicity in T47D and MCF-7 cells, but not in SK-Br3 cells, whereas preincubation with OA failed to increase paclitaxel effectiveness in all three cell lines. For comparison, the effects of other fatty acids on paclitaxel chemosensitivity were examined: GLA was the most potent at enhancing paclitaxel cytotoxicity, followed by alpha-linolenic acid (ALA; 18:3n.3), eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3), whereas linoleic acid (LA; 18:2n-6) did not increase paclitaxel toxicity. These findings provide experimental support for the use of fatty acids as modulators of tumour cell chemosensitivity in paclitaxel-based therapy.
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PMID:Effects of gamma-linolenic acid and oleic acid on paclitaxel cytotoxicity in human breast cancer cells. 1123 64

The estrogenicity of Black Cohosh (Cimicifuga racemosa, CR) was tested in vivo and in vitro and its effect on estrogen receptor (ER) level of human breast cancer MCF-7 cells were investigated. Based on the body weight of animals, 75, 150 and 300 mg/kg of CR were administered by tube feeding to immature female mice for 14 days. Estrus was observed and the uterine and ovary weights of mice were measured. The optimal dose of CR for the growth of MCF-7 cells was screened by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay. Subsequently, Growth curves of MCF-7 cells in blank control, 4.75 micrograms/L of CR and 0.3 nmol/L of 17 beta-estradiol groups were observed for 5 days. ER level in MCF-7 cells was analyzed by indirect immunofluorescence assay in flow cytometry. The results showed that uterine weight increased with the increasing dosage of CR and the days of estrus was significantly prolonged in the 300 mg/kg group (P < 0.05). The concentration of CR at 4.75 micrograms/L showed the strongest enhancement effects (64.7%). The doubling time (TD) of cell growth in CR group and 17 beta-estradiol group were 32.1 h and 31.7 h respectively, which were shorter than that of blank control (TD = 35.3 h). Additionally, 4.75 micrograms/L of CR significantly increased ER levels compared with the blank control (P < 0.01). Taking all the results together, CR has an estrogen-like action. The enhancing effect of CR on ER level is one of the potential mechanisms involved with its therapeutic role in climacteric syndrome.
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PMID:[Estrogenicity of black cohosh (Cimicifuga racemosa) and its effect on estrogen receptor level in human breast cancer MCF-7 cells]. 1132 55

Diallyl disulfide (DADS) is an oil-soluble organosulfur compound found in garlic. The effect of synthetic DADS on the growth of estrogen receptor (ER)-positive (KPL-1 and MCF-7) and -negative (MDA-MB-231 and MKL-F) human breast cancer cell lines was examined. In an in vitro MTT assay, regardless of ER status, DADS at an IC(50) of 1.8-18.1 microM after 72 h incubation caused inhibition of growth in all four cell lines examined. Growth inhibition was due to apoptosis as seen by the appearance of a sub G1 fraction. In MDA-MB-231 cells, the apoptosis cascade comprised up-regulation of Bax protein (142%), down-regulation of Bcl-X(L) protein (38%) and activation of caspase-3 (438%) compared with controls. In an in vivo assay by orthotopic (right thoracic mammary fat pad) transplantation of KPL-1 cells in female nude mice, intraperitoneal injection of 1 or 2 mg DADS three times a week from the day of tumor cell inoculation until the end of the experiment (after 35 days) caused growth retardation and 43% reductions in primary tumor weight, respectively, compared with DADS-untreated mice without apparent side effects. Cell proliferation as evaluated by proliferating cell nuclear antigen (PCNA)-labeling in transplanted tumor of DADS-untreated mice was 59.6%, and 1 and 2 mg DADS-treated mice was 44.6 and 44.5%, respectively. In MDA-MB-231 cells, DADS antagonized the effect of linoleic acid (LA), a potent breast cancer cell stimulator (at DADS = 1.8 microM and LA > or = 6.5x10(2) microM concentration), and synergized the effect of eicosapentaenoic acid (EPA), a potent breast cancer cell suppressor (at DADS >3 x 10(-3) microM and EPA > 6.3 x 10(-1) microM concentration). Thus, DADS could be a promising anticancer agent for both hormone-dependent and -independent breast cancers, and may harmonize with polyunsaturated fatty acids known as modulators of breast cancer cell growth.
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PMID:Growth inhibitory effects of diallyl disulfide on human breast cancer cell lines. 1137 95

The aim of this study was to examine MDR1 expression product P-glycoprotein (Pgp) and study the effect and mechanism of tea polyphenol (TP) in reversion of multidrug resistance (MDR) in carcinoma cell lines. Immunocytochemical method was used for qualitative detection of Pgp. A comparative study of cytotoxicity and multidrug resistance reversion effect was made by MTT assay for tea polyphenol and quinidine in MCF-7 and MCF-7/Adr cell lines. The multidrug resistance reversion effect and mechanism were studied by measuring the uptake of 99mTc-tetrofosmin in the carcinoma cell lines. (1) The Pgp overexpression in MCF-7/Adr cells was found to be strong positive, while the Pgp expression of MCF-7 was negative. (2) Although both tea polyphenol and quinidine could not remarkably change the toxicity of adriamycin to MCF-7, they could improve the sensitivity of MCF-7/Adr to adriamycin. The reversion index of tea polyphenol and quinidine was 3 and 10 respectively. (3) The cellular uptake of 99mTc-tetrofosmin was remarkably lower in MCF-7/Adr than in MCF-7. The uptake of 99mTc-tetrofosmin in MCF-7/Adr exhibited a 4, 13, 16 fold increase in the presence of 200, 400 and 500 microg/ml of tea polyphenol respectively. The uptake of 99mTc-tetrofosmin in MCF-7/Adr exhibited only a 4-fold increase in the presence of 200 microM of quinidine. Immunocytochemistry can detect P-glycoprotein expression level qualitatively. Tea polyphenol is not only an anti-tumor agent, but also a multidrug resistant modulator similar to quinidine. The multidrug resistance reversion mechanism of tea polyphenol seems to be its inhibition of the activity of P-glycoprotein. Tea polyphenol has the advantage of very low toxicity in tumor treatment.
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PMID:Study of tea polyphenol as a reversal agent for carcinoma cell lines' multidrug resistance (study of TP as a MDR reversal agent). 1151 57

Antibiotic G0069A, produced by a Streptomyces strain isolated from a soil sample collected in Yunnan Province, China, has been verified as a clavam peptide. Determined by MTT assay, G0069A showed highly potent cytotoxicity to cancer cells with multidrug resistance. The IC50 values of G0069A to KB and KB/VCR cells were 0.60 and 0.46 mumol.L-1, and to MCF-7 and MCF-7/ADM cells were 1.4 and 1.2 mumol.L-1, respectively. G0069A displayed equally potent cytotoxicity to the parent cell lines and their resistant sublines. When administered by i.v. or i.p. route at tolerable doses, G0069A exhibited markedly inhibitory effect on the growth of sarcoma 180 and hepatoma 22 in mice. At dose level of 3 mg.kg-1, i.v., x3, sarcoma 180 and hepatoma 22 were suppressed by 87%(P < 0.01) and 72%(P < 0.01), respectively. The results indicate that G0069A is a beta-lactam antibiotic showing antitumor activity.
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PMID:[Antitumor activity of the clavam peptide antibiotic G0069A]. 1159 87

P-glycoprotein (P-gp) overexpression by tumor cells imparts resistance to multiple antineoplastic chemotherapeutic agents (multiple drug resistance). Treatment of tumor cells with chemotherapeutic agents such as anthracyclines, epipodophyllotoxins, and Vinca alkaloids results in induction of P-gp expression. This study was performed to determine if clinically relevant antimicrobial drugs (i.e., drugs that are used to treat bacterial infections in cancer patients) other than antineoplastic agents can induce expression of P-gp in MCF-7 breast carcinoma cells. Expression of P-gp and MDR1 mRNA was determined in samples from MCF-7 cells that were treated in culture with doxorubicin (positive control) and the antimicrobial drugs doxycycline, piperacillin, and cefoperazone. The functional status of P-gp was assessed using laser cytometry to determine intracellular doxorubicin concentrations. The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay was used to determine if the cytotoxicity of experimental drugs was related to their ability to induce P-gp expression. MCF-7 cells treated with doxycycline (MCF-7/doxy) were stimulated to overexpress P-gp, whereas cells treated with piperacillin and cefoperazone did not overexpress P-gp. MCF-7/doxy cells were compared to a positive-control subline, MCF-7/Adr, previously selected for doxorubicin resistance, and to MCF-7 cells treated with doxorubicin (MCF-7/doxo). All three sublines overexpressed P-gp and MDR1 mRNA and accumulated less intracellular doxorubicin than did control MCF-7 cells. P-gp expression was induced only by experimental drugs that were cytotoxic (doxorubicin and doxycycline). Doxycycline, a drug that has been used for treatment of bacterial infections in cancer patients, can induce functional P-gp expression in cancer cells, resulting in multidrug resistance.
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PMID:Doxycycline induces expression of P glycoprotein in MCF-7 breast carcinoma cells. 1185 Feb 58

To evaluate whether leptin plays a putative role in breast tumorigenesis, we studied the expression of its long and short receptor isoforms in various tumoral breast tissues. We applied semiquantitative RT-PCR method to RNA extracted from 20 breast cancer biopsies and two human breast cancer cell lines (T47-D and MCF-7). Our results showed the expression of both leptin receptor transcripts in all tumoral tissues examined. By in situ hybridization experiments, we localized leptin receptors in proliferating epithelial cells. Study of leptin effects on human breast cancer cells growth was performed by [3H]-thymidine incorporation method and colorimetric MTT assay. We demonstrated that leptin (50-100 ng/ml) significantly stimulates proliferation of the human breast cancer cell line T47-D (P<0.05). Western blot analysis indicated that leptin induces a time-dependent activation of mitogen-activated protein kinases (MAPKinase) 1 and 2 in T47-D cell line. Moreover, the specific MAPK-inhibitor PD 98059 blocked cell proliferation induced by leptin. In conclusion, we demonstrate that leptin receptors are expressed in breast cancer and that leptin induces proliferation in the T47-D cell line via activation of the MAPKinases pathway. These data suggest that leptin and its receptors may be implicated in mammary cell proliferation and in breast cancer pathogenesis.
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PMID:Identification of leptin receptors in human breast cancer: functional activity in the T47-D breast cancer cell line. 1191 59

Secretion of human chorionic gonadotropin (hCG) during pregnancy induces differentiation of the mammary gland, thereby making breast tissue less susceptible to carcinogenesis. HCG binds to specific hCG receptors on mammary epithelial cells inducing changes in gene expression that can inhibit cell proliferation and, therefore, interfere with tumorigenesis. Since breast cancer cells also contain a relatively high level of the hCG receptor, hCG has potential as a therapeutic agent. We postulated that hCG might also enhance the radiosensitivity of breast cancer cells and, therefore, be useful as an adjunctive therapy. In the present study, MCF-7 breast cancer cells grown in cell culture were treated with hCG (0.2-5 IU/ml) for 24 h prior to exposing the cells to 0 Gy, 3 Gy, 4 Gy, or 5 Gy of radiation. Following irradiation, the MCF-7 cells were incubated either in the presence or absence of hCG. Cell survival was monitored with an MTT assay 1 day, 4 days, and 7 days after irradiation. All of the concentrations of hCG tested enhanced radiosensitivity of MCF-7 cells. The maximum enhancement occurred with MCF-7 cells that had been exposed to 2 IU/ml of hCG for at least 24 h prior to irradiation with 4 Gy. The use of higher concentrations of hCG or a higher dose of radiation did not increase the enhancement effect. Treatment of MCF-7 cells with hCG for only 24 h was sufficient to achieve the maximum effect. However, maintaining the cells in hCG beyond 24 h increased the effectiveness of the lowest hCG concentration. Using a linear-quadratic equation to analyze the data, we determined that the use of hCG would result in an 8-10% reduction in MCF-7 cell survival at a dose of 2 Gy, a typical dose used in conventional cancer therapy.
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PMID:Enhancement of radiosensitivity of the MCF-7 breast cancer cell line with human chorionic gonadotropin. 1200 Feb 19


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