Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0276241 (MCF)
 28,353 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Competitive inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase are commonly used in the clinic to treat hypercholesterolemia and have been reported to exert antitumor effects. Cerivastatin is a novel, synthetic and the most pharmacologically potent inhibitor of HMG-CoA reductase. We decided to examine the cytostatic/cytotoxic activity of cerivastatin against human breast cancer cell lines and to test whether the effects of cerivastatin could be potentiated by doxorubicin and cisplatin. Cytostatic/cytotoxic effects of cerivastatin used alone or in the combination with chemotherapeutics were measured with MTT assay. The cell cycle distribution and apoptosis induction were evaluated with flow cytometer. The expression of p21 and p27 cyclin-dependent kinase inhibitors was measured with Western blotting. Isobologram analysis was performed to study the drug interactions. We observed that cerivastatin exerts cytostatic/cytotoxic effects against four human tumor cell lines (T-47D, T4-2, MDA-MB-231, MCF-7). We also demonstrated that cerivastatin exerts growth inhibitory effect through induction of p21 cyclin-dependent kinase inhibitor and inhibition of cell cycle progression. In the two tumor cell lines studied, one sensitive (MDA-MB-231) and one moderately resistant (T4-2) to the cytostatic/cytotoxic effects of cerivastatin we examined the effects of combined treatment with cerivastatin and either doxorubicin or cisplatin. Cerivastatin potentiated cytostatic/cytotoxic effects of cisplatin against T4-2 cells and those of doxorubicin against both cell lines. In T4-2 cells the interaction between doxorubicin and cerivastatin and between cisplatin and cerivastatin was found to be synergistic. Altogether, these studies indicate that cerivastatin is another HMG-CoA reductase inhibitor with potent antitumor effects.
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PMID:Cerivastatin demonstrates enhanced antitumor activity against human breast cancer cell lines when used in combination with doxorubicin or cisplatin. 1506 36

Pseudogenes are classically thought of as nonfunctional DNA sequences due to their inability to be translated, or to produce a functional protein. Gap junctions, a multiprotein complex made of proteins called connexins, are involved in intercellular communication and are deregulated in many cancers. Connexin43 (Cx43) is the only connexin for which a pseudogene has been reported so far. The Cx43 pseudogene (PsiCx43) has all of the features of an expressed gene. We identified the presence of a PsiCx43 mRNA transcript in several cancer cell lines and in none of the normal mammary epithelial cells studied. Using an in vitro translation assay, we found that the PsiCx43 coding plasmid could be translated into a 43 kDa protein. This was further confirmed by expressing a PsiCx43-green fluorescence protein fusion protein in breast cancer MCF-7 cells. We then examined the functional significance of the PsiCx43. In both MTT growth and colony formation assays, significant growth inhibition was observed, a feature common to cells overexpressing the Cx43 gene. However, using a scrape-loading assay, we could not detect any effect on gap junctional intercellular communication. Based on our findings, PsiCx43 joins and enlarges the thus far restricted group of functionally transcribed and translated pseudogenes.
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PMID:Connexin43 pseudogene is expressed in tumor cells and inhibits growth. 1512 29

The omega-6 polyunsaturated fatty acid gamma-linolenic acid (GLA; 18:3n-6) has raised recent interest as novel anti-cancer agent as it possesses effective tumoricidal properties while not inducing damage to normal cells or creating harmful systemic side effects. The taxane docetaxel (Taxotere) is currently one of the most active microtubule-interfering agents for breast cancer. Despite this encouraging therapeutical potential, the clinical use of taxanes involves problems related to the solubility, toxicity and development of drug resistance, which may be partially dependent on the expression of HER-2/neu oncogene. Current trends in the treatment of human tumors are for drug combinations that result in improved responses as well as the ability to use less toxic concentrations of the drugs. Here, we examined the cytotoxic effects of GLA in combination with docetaxel against estrogen-dependent (MCF-7) and estrogen-independent (MDA-MB-231 and SK-Br3) human breast carcinoma cell lines. The cells were exposed simultaneously to GLA and docetaxel or sequentially to GLA followed by docetaxel for 24 h. Cytotoxicity was evaluated by the MTT assay, and the nature of the interactions between GLA and docetaxel (antagonism, additivity, and synergism) was analyzed by median effect and isobologram analyses. Interaction assessment showed that concurrent exposure to GLA plus docetaxel for 24 h resulted in synergism for MCF-7 and MDA-MB-231 cells, whereas an additive effect was observed in SK-Br3 cells. When exposure to GLA (24 and 48 h) was followed sequentially by docetaxel (24 h) a synergistic effect was observed in MDA-MB-231 and SK-Br3 cells, whereas an additive effect was found in MCF-7 cells. GLA-mediated increase in docetaxel cytotoxicity was only marginally abolished by Vitamin E, a lipid peroxidation inhibitor. Moreover, simultaneous exposure to GLA and docetaxel in the presence of the anti-oxidant Vitamin E also resulted in synergism, suggesting a limited influence of the oxidative status of GLA in achieving potentiation of docetaxel-induced cytotoxicity. Further experiments showed that GLA markedly decreased the expression of p185HER-2/neu oncoprotein in MCF-7 breast cancer cells (</=85%), and RT-PCR analysis revealed that HER-2/neu mRNA was selectively decreased in a concentration-dependent manner following GLA treatment. Therefore, our results show that the fatty acid GLA enhances the cytotoxicity of docetaxel in human breast cancer cells by mechanisms other than lipoperoxidation, and that GLA-induced transcriptional repression of HER-2/neu oncogene might be one component of the mechanisms of this interaction.
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PMID:Omega-6 polyunsaturated fatty acid gamma-linolenic acid (18:3n-6) enhances docetaxel (Taxotere) cytotoxicity in human breast carcinoma cells: Relationship to lipid peroxidation and HER-2/neu expression. 1513 62

Melissa officinalis L (lemon balm) is a traditional herbal medicine used widely as a mild sedative, spasmolytic and antibacterial agent. This paper focuses on the analysis of the chemical composition and the biological activities of M. officinalis essential oil obtained under controlled harvesting and drying conditions. An in-vitro cytotoxicity assay using MTT indicated that this oil was very effective against a series of human cancer cell lines (A549, MCF-7, Caco-2, HL-60, K562) and a mouse cell line (B16F10). This oil possessed antioxidant activity, as evidenced by reduction of 1,1-diphenyl-2-picryl-hydrazyl (DPPH). These results pointed to the potential use of M. officinalis essential oil as an antitumoral agent.
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PMID:Melissa officinalis L. essential oil: antitumoral and antioxidant activities. 1514 47

This study was designed to observe whether the rates of apoptosis induced in the breast cancer cell line MCF-7 by 5-fluorouracil (5-FU) could be enhanced by transfecting bcl-2 antisense oligonucleotide (ASODN). In our experiment, bcl-2 ASODNs and control ODNs including untreated control, sense ODN and scrambled ODN, were transfected into MCF-7 cells. Changes in expression of the bcl-2 gene were examined by Western blot; cell growths were detected by MTT assay, and apoptosis rates were detected by flow cytometry (FCM). Expression of bcl-2 protein after transfection of bcl-2 ASODN was significantly lower than control ODNs. Moreover, incubation of MCF-7 with bcl-2 ASODN prior to 5-FU treatment caused remarkable loss of viable cells compared with all other control ODNs (P < 0.01). FCM showed the apoptosis rates for ASODN, untreated control, sense ODN and scrambled ODN (29.8 +/- 7.4)%, (8.0 +/- 2.3)%, (15.0 +/- 5.1)% and (16.5 +/- 7.1)%, respectively. Compared with control ODNs, ASODN achieved the strongest effect in terms of enhancing apoptosis (P < 0.01). These results suggest that combining bcl-2 ASODN with 5-FU led to synergistic cytotoxicity.
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PMID:Chemosensitization of breast carcinoma cells with the use of bcl-2 antisense oligodeoxynucleotide. 1517 26

A reduced incidence of different types of cancer has been linked to consumption of Brassica vegetables, and there is evidence that glucosinolates (GSLs) and their hydrolysis products play a role in reducing cancer risk. Wasabi (Wasabia japonica) and horseradish (Armoracia rusticana), both Brassica vegetables, are widely used condiments both in Japanese cuisine and in the United States. Desulfosinigrin (DSS) (1) was isolated from a commercially available wasabi powder and from fresh wasabi roots. Sinigrin (2) was isolated from horseradish roots. DSS and sinigrin were evaluated for their inhibitory effects on cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes, on lipid peroxidation, and on the proliferation of human colon (HCT-116), breast (MCF-7), lung (NCIH460), and central nervous system (CNS, SF-268) cancer cell lines. DSS did not inhibit COX enzymes or lipid peroxidation at 250 microg/ml. Sinigrin inhibited lipid peroxidation by 71% at 250 microg/ml. However, DSS promoted the growth of HCT-116 (colon) and NCI H460 (lung) human cancer cells as determined by the MTT assay in a concentration-dependent manner. At 3.72 microg/ml, a 27% increase in the number of viable human HCT-116 colon cancer cells was observed; the corresponding increases at 7.50 and 15 microg/ml were 42 and 69%, respectively. At 60 microg/ml, DSS doubled the number of HCT-16 colon cancer cells. For NCI H460 human lung cancer cells, DSS at 60 microg/ml increased the cell number by 20%. Sinigrin showed no proliferating effect on the tumor cells tested. This is the first report of the tumor cell-proliferating activity by a desulfoglucosinolate, the biosynthetic precursor of GSLs found in Brassica spp.
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PMID:Colon cancer proliferating desulfosinigrin in wasabi (Wasabia japonica). 1523 56

Design, syntheses and relative in vitro gene delivery efficacies of six novel cationic glycolipids 1-6 containing open-form galactosyl units in CHO, COS-1, MCF-7 and A549 cells are described. The results of the present structure-activity investigation convincingly demonstrate that the in vitro gene delivery efficacies of galactosylated cationic glycolipids are strikingly dependent on the absence of a spacer-arm between the open-form galactose and the positively charged nitrogen atom in their headgroup region. While the cationic glycolipids 1-3 with no headgroup spacer unit between the positively charged nitrogen and galactose showed high in vitro gene transfer efficacies in all four cells (lipids 1 and 2 with myristyl and palmityl tails, respectively, being the most efficacious), lipids 4-6 with five-carbon spacer units between the quaternized nitrogen and galactose heads were essentially transfection incompetent. The transfection inhibiting role of the five-carbon spacer unit in the headgroup region of the present novel class of cationic lipids was demonstrated by both beta-galactosidase reporter gene expression and histochemical X-gal staining assays. Results of MTT assay-based cell viability measurements in representative MCF7 cells show that cell viabilities of lipoplexes (lipid:DNA complexes) prepared from all the lipids 1-6 are remarkably high. Thus, possibilities of differential cellular cytotoxicities playing any key role behind the strikingly contrasting transfection properties of lipids 1-3 with no spacer and lipids 4-6 with a spacer unit in the headgroup regions was ruled out. Electrophoresis gel patterns in DNase I sensitivity assays are consistent with more free DNA (accessible to DNase I) being present in lipoplexes of lipids 4-6 than in lipoplexes of lipids 1-3. Thus, the results of our DNase I protection experiments support the notion that enhanced degradation of DNA associated with lipoplexes of lipids 4-6 may play an important role in abolishing their in vitro gene transfer efficacies.
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PMID:Spacer-arm modulated gene delivery efficacy of novel cationic glycolipids: design, synthesis, and in vitro transfection biology. 1526 33

In recent years, breast cancers have aroused much concern. Together with a growing incidence all over the world, the development of drug resistance to tamoxifen, the most commonly prescribed chemotherapeutic drug for breast cancer patients, has highlighted the importance of developing a new chemotherapeutic drug in combating breast cancer. With the aim of treating breast cancers, the anti-tumor effects of arsenic trioxide in MCF-7 cells have been studied. MCF-7 cells are estrogen responsive cells which mimic breast cancers at the early stage. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and direct cell counting were used to measure cell proliferation. The mechanisms of action were elucidated through the measurement of estrogen receptor (ER) binding, mRNA and protein levels of ERalpha and its activity. We have demonstrated that arsenic trioxide was capable of reducing cell survival in MCF-7 cells via the suppression of the estrogen-induced growth stimulatory effects in MCF-7 cells. Arsenic trioxide was shown to suppress the action of estrogen through the regulation of the ERalpha signaling pathway. Arsenic trioxide could down-regulate ERalpha mRNA and protein levels without competing with estrogen for ERalpha binding. Arsenic trioxide also inhibited the transcription activity mediated by the ERalpha signaling pathway and ultimately it down-regulated c-myc protein expression and inhibited cell entry to S phase under estrogen's stimulation. In conclusion, arsenic trioxide could inhibit the growth of MCF-7 cells by reducing the growth stimulatory effect of estrogen. As estrogen is a primary risk factor in promoting the growth of breast tumor cells, the anti-estrogenicity exhibited by arsenic trioxide sheds light on the therapy of breast cancer.
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PMID:Suppression of cell proliferation and regulation of estrogen receptor alpha signaling pathway by arsenic trioxide on human breast cancer MCF-7 cells. 1528 93

Overexpression of P-glycoprotein (P-gp) by tumours results in multidrug resistance (MDR) to structurally and functionally unrelated chemotherapeutic drugs. Combined therapy with MDR-related cytotoxins and MDR modulators is a promising strategy to overcome clinical MDR. This study was performed to explore the MDR reversal activity of a novel compound 2-[4-(2-pyridin-2-yl-vinyl) phenyl]-4,5-bis-(4-N,N-diethylaminophenyl)-1(H)-imidazole (FG020318) in-vitro and in-vivo. Tetrazolium (MTT) assay was used to evaluate the ability of FG020318 to reverse drug resistance in two P-gp-expressing tumour cell lines, KBv200 and MCF-7/adr. Intracellular doxorubicin accumulation was determined by fluorescence spectrophotometry in MCF-7/adr cell line. The effect of FG020318 on P-gp function was demonstrated by rhodamine 123 (Rh123) accumulation in KBv200 cells. KBv200 cell xenograft models were established to study the in-vivo effect of FG020318 on reversing MDR. FG020318 was not cytotoxic by itself against P-gp expressing KBv200 cells and MCF-7/adr cells and their parental drug-sensitive KB cells and MCF-7 cells. FG020318 could significantly increase the sensitivity of MDR cells to antitumour drugs including doxorubicin and vincristine in MCF-7/adr cells and KBv200 cells, respectively. It was much stronger than the positive control verapamil in reversal of MDR. FG020318 also increased the intracellular accumulation of doxorubicin in a concentration-dependent manner in MCF-7/adr cells, but did not affect the accumulation of doxorubicin in drug-sensitive MCF-7 cells. The Rh123 accumulation in resistant KBv200 cells was also increased by the addition of FG020318, but Rh123 accumulation was not affected by FG020318 in drug-sensitive KB cells. FG020318 potentiated the antitumour activity of vincristine to KBv200 xenografts and was an efficacious modulator in-vivo. Our results suggested that FG020318 was a highly potent, efficacious MDR modulator not only in-vitro but also in-vivo. The reversal of drug resistance by FG020318 was probably related to the increased anticancer drug accumulation and its inhibition of P-gp function of MDR tumour cells.
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PMID:Reversal of P-gp mediated multidrug resistance in-vitro and in-vivo by FG020318. 1528 52

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.
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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


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