Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously shown that beta-all trans retinoic acid (RA) inhibits macrocellular growth of a multicellular tumor spheroid model for squamous carcinoma, as measured by spheroid size, but allows for continuing DNA synthesis and cell cycle progression, the two being reconciled by a cell death effect. DNA synthesis in the presence of growth inhibition suggested a rationale for examining combination chemotherapy with RA-inhibited cells. To this aim, we have extended this observation to a series of 8 squamous carcinoma cell lines. Cells were treated with 1 microM RA for 7 days and cell growth parameters monitored. Although growth inhibition ranged from 0% (A431) to approx. 80% (MDA 886Ln), [3H]-thymidine incorporation (cpm/microgram protein) and percent S-phase (by flow cytometry) in 7-day RA-treated cells was equal or higher than in their control vehicle-treated cells in 7/8 SCC cell lines. Thus RA-induced growth inhibition is not just cytostasis. Combination therapy was examined with MDA 886Ln, MDA 686Ln, 1483 and A431 cells pre-treated for 7 days with 1 microM RA followed by cisplatin or 5-fluorouracil treatment. An increased effectiveness for the combination was shown using 5-day tetrazolium dye (MTT) growth assays when cells were growth-inhibited by RA. Computerized analysis of data using median-effect and isobologram techniques indicated that the interaction of RA with these chemotherapeutic agents was synergistic. With squamous carcinoma, RA treatment inhibits growth while allowing for continuing DNA synthesis, and these RA-treated, growth-inhibited cells exhibit increased sensitivity to chemotherapeutic agents.
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PMID:Modulation of growth and proliferation in squamous cell carcinoma by retinoic acid: a rationale for combination therapy with chemotherapeutic agents. 772 55

Effects of gamma-irradiation, given in the range of 5 to 30 Gy on Caski cells (Epitheloid carcinoma from the cervix) were investigated by the MTT (3-(4,5-dimethylthiazol-2-yl) -2, 5-diphenyl tetrazolium bromide) method. Results were compared with data assessed simultaneously from cell number counts. The sizes of cells irradiated with 10 to 30 Gy were larger than those of unirradiated ones, and each irradiated cell reduced a larger amount of MTT than did each unirradiated cell. Irradiation in the above range, therefore causes Caski cells to lose their ability to divide, but the effect on the mitochondria was very slight. Application of the MTT method to the irradiated cells should be done with care. Because, in the irradiated cells depending on the irradiation dose, the MTT activity does not correlate to the cell number.
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PMID:Gamma irradiation effects on cultured cells: investigated by the MTT method. 775 4

A polyacetylenic alcohol, panaxytriol, isolated from Panax ginseng C. A. Meyer inhibits both tumor cell growth in vitro and the growth of B16 melanoma transplanted into mice. Our preliminary studies indicated that panaxytriol localizes to the mitochondria in human breast carcinoma cells (Breast M25-SF). This study focused on the effects of panaxytriol on mitochondrial structures and function in Breast M25-SF. The results indicate that panaxytriol rapidly inhibits cellular respiration and disrupts cellular energy balance in Breast M25-SF. At concentrations between 11.3 and 180 microM, panaxytriol causes a dose-dependent inhibition of the conversion of the tetrazolium (MTT assay) by mitochondrial dehydrogenase within 2 h. A 1-h treatment with 180 microM panaxytriol causes a significant loss of rhodamine-123 from cells with mitochondria prestained with rhodamine-123 (by flow cytometry). Specific toxic changes were observed by electron microscopy in the mitochondria of Breast M25-SF within 1 h after treatment with more than 180 microM panaxytriol. These data indicate that 180 microM panxytriol rapidly disrupts cellular energy balance and respiration in Breast M25-SF and suggest that panaxytriol may lower cellular ATP concentrations. After treatment with 180 microM panaxytriol, cellular ATP levels were 40% of those in control cells after 1 h. ATP depletion preceded the loss of cellular viability. Neither ATP depletion nor cytolysis was found in human erythrocytes that have no mitochondria. Thus, ATP depletion resulting from a direct inhibition of mitochondrial respiration is a critical early event in the cytotoxicity of panaxytriol.
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PMID:A possible mechanism for the cytotoxicity of a polyacetylenic alcohol, panaxytriol: inhibition of mitochondrial respiration. 782 71

We describe the selection of 3 new multidrug-resistant cell lines derived from tumor cells of different metastatic phenotypes within the Dunning R3327 model of rat prostatic carcinoma. Cell lines of weak (AT2) and strong (AT3 and MAT-LyLu) metastatic behavior were cultured in vitro and challenged with doxorubicin at progressively increasing concentrations. Chemosensitivity was determined colorimetrically by release of precipitated formazan pigment (MTT assay). Expression of the multidrug-resistance glycoprotein (P-170) was monitored immunocytochemically and by Western blotting using monoclonal antibody C219. The behavior of the parental and resultant drug-resistant cells was assessed by their growth in syngeneic rats. Doxorubicin challenge of the initially drug-sensitive parental prostatic carcinoma cell lines resulted in the rapid development of multidrug resistance together with simultaneous expression of P-glycoprotein. While lung and lymph-node metastases developed in host animals inoculated with parental AT3 and MAT-LyLu cells, no metastases developed in the multidrug-resistant progeny of these cell lines. This study has shown that Dunning rat prostate-carcinoma cell lines, previously sensitive to different cytotoxic agents, rapidly become multidrug-resistant and express P-glycoprotein following exposure to doxorubicin. Furthermore, development of multidrug resistance is associated with a less aggressive tumor phenotype and loss of metastatic potential. Nevertheless, it is unlikely that the non-metastatic phenotype of Dunning rat prostatic carcinoma cells is solely associated with expression of P-glycoprotein. These new multidrug-resistant cell lines exhibiting an altered behavioral phenotype will provide a valuable model with which to analyze the relationship between expression of P-glycoprotein and the metastatic phenotype of prostatic carcinoma cells.
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PMID:Establishment and in vivo characterization of multidrug-resistant dunning R3327 rat prostate-carcinoma cell-lines. 791 Aug 10

The role of estrogenic hormones on the induction of drug resistance was studied in cervical cancer cell lines, SiHa and Caski. After the cells were inoculated with estradiol (E2) or diethylstilbestrol (DES) in various dosages, the cell survival rates with adriamycin treatment were examined by MTT (3-[4,5-dimethyl-thiazole-2-yl]-2,5-diphenyl-tetrazolium-bromide) test and the intracellular accumulation of adriamycin was evaluated by flow cytometry. In the same condition, the expression of multidrug resistance gene-1 (mdr-1 gene) was detected either by Northern blot hybridization for mdr-1 mRNA or by immunoblot for P-glycoprotein 170. The data in this study indicated that estrogenic hormones had the capacity to induce drug resistance in cervical carcinoma cell lines. When cells were treated with estrogenic hormones and adriamycin simultaneously, the intracellular accumulation of adriamycin declined and corresponded with the drug resistance. Since the expression of the mdr-1 gene induced by E2 or DES results in drug resistance, it is suggested that the mdr-1 gene in SiHa cells may contain the estrogenic responsive element (ERE) in its regulatory region. However, the mechanism of drug resistance induced by estrogenic hormones in Caski cells is different from SiHa cells due to the absence of mdr-1 gene expression. Despite that, this experiment may provide a model to investigate the relationships between estrogenic hormones and drug resistance in other female genital cancers.
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PMID:The induction of multidrug resistance in human cervical carcinoma cell lines by estrogenic hormones. 791 38

We evaluated the anti-tumour activity of human recombinant interferon-alpha (IFN-alpha) on two human squamous carcinoma of tongue cell lines (T2/CUHK and PWH-S1). The in vitro cytotoxicity was monitored by MTT assay. Continuous exposure to IFN-alpha alone at 500 IU/ml for 48 h produced inhibitory growth of 30% and 7% on T2/CUHK and PWH-S1 cell lines respectively. The ID50 of T2/CUHK cells was approximately 2500 IU/ml. PWH-S1 cells were resistant to treatment with interferon-alpha as 500 IU/ml IFN-alpha gave only 10% growth inhibition on PWH-S1 cells. IFN-alpha increased the anti-neoplastic activity of cisplatin and 5-FU against T2/CUHK cells, but the effect was less evident in PWH-S1 cells. Our findings support the further evaluation of IFN-alpha as a potent anti-proliferative cytokine therapy that may act synergistically with conventional chemotherapeutic agents for the treatment of squamous carcinoma of head and neck.
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PMID:Anti-proliferative activity of interferon-alpha on human squamous carcinoma of tongue cell lines. 792 2

The growth-inhibitory effect of interleukin-4 (IL-4) was investigated in a panel of 7 human colorectal-carcinoma cell lines. In 5 cell lines (HT29, WiDr, LS411N, LS513, LS1034) a dose-dependent reduction of proliferation was documented. At 100 U/ml, IL-4 inhibited thymidine incorporation between 45 and 75% and MTT conversion (26 to 41%). The ability of LS513 and WiDr cells to form colonies after IL-4 treatment was reduced by 85 and 62% respectively. LS513 was the most sensitive cell line, with IL-4 inducing half-maximal inhibition at 5 to 6 U/ml. The inhibitory effect of IL-4 was completely neutralized by anti-IL-4 antibodies. Northern-blot analysis revealed the presence of IL-4-receptor (IL-4R) mRNA in all cell lines. The membrane expression of the 130-kDa IL-4R was assessed by FACS, utilizing an anti-IL-4R monoclonal antibody and was confirmed by biotinylated IL-4 binding. Our results attribute an important role for IL-4 as a negative regulator of colorectal-carcinoma cell growth, thus indicating a possible avenue for intervention in this disease.
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PMID:Growth inhibition of human colorectal-carcinoma cells by interleukin-4 and expression of functional interleukin-4 receptors. 792 55

Bryostatin 1 (Bryo) is a naturally occurring macrocyclic lactone with antineoplastic activity. Like the phorbol ester 12-O-tetradecanoyl-phorbol 13-acetate (TPA) it directly activates the calcium- and phospholipid-dependent protein kinase C (PKC), thus generating a number of different cellular responses. We investigated the effects of Bryo and TPA on DNA synthesis, proliferation, viability and c-myc protooncogene expression of the human carcinoma cell lines COLO-320, MEL-HO, and KB-3-1. TPA inhibited [3H]-thymidine incorporation in all three cell lines in a dose-dependent manner, whereas Bryo only inhibited the DNA synthesis in MEL-HO, but not in KB-3-1 and COLO-320 cells. Within the concentration ranges used, TPA and Bryo were found to have a low toxicity. Counting of the cells confirmed the observed inhibition of cell proliferation. However, the enzymatic conversion of MTT, applied as a colorimetric proliferation assay, was not significantly affected by both biomodulators. Time-course experiments revealed a rapid onset of the inhibitory effect on DNA synthesis. Bryo was further able to antagonize the TPA-mediated effects on proliferation suggesting an (at least partially) different mode of action of these PKC activators. Incubation of MEL-HO and COLO-320 cells with either of the two biomodulators resulted in a rapid and strong increase of c-myc mRNA. The present study emphasizes Bryo as an interesting, natural substance for the study of PKC-mediated biological effects.
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PMID:Different biological effects of the two protein kinase C activators bryostatin-1 and TPA on human carcinoma cell lines. 796 Jun

We investigated the production of leukemia inhibitory factor (LIF) by human carcinoma cell lines. LIF mRNA was detected by Northern blot analysis in all 24 carcinoma cell lines of the lung, breast, stomach, colon, liver, gallbladder, pancreas and melanocytes. Seventeen of them (70.8%) secreted LIF in the culture supernatant (range: 40.4-3990.3 pg/ml, mean +/- SEM: 611.8 +/- 262.9 pg/ml). Biologic activity of LIF was confirmed in the culture supernatant of carcinoma cell lines by the MTT assay using M1 cells. The present results showed that human carcinoma cell lines are constitutively producing biologically active LIF. The possible biological significance of LIF produced by cancer cells is discussed.
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PMID:Human carcinoma cell lines produce biologically active leukemia inhibitory factor (LIF). 799 57

Using 3-(4,5-dimethythiazole)-2,5-diphenyltetrazolium bromide (MTT) method, the effect of probimane (Pro) on doxorubicin (Dox) cytotoxicity was studied. Pro 0.313, 0.625, and 1.25 micrograms.ml-1 potentiated cytotoxicity of Dox in Ehrlich ascites carcinoma (EAC) cells. Incubation of EAC cells with Dox 10 micrograms.ml-1 and Pro 116.5, 233, and 466 micrograms.ml-1 resulted in an increase in intracellular drug accumulation from 0.69 +/- 0.06 to 1.08 +/- 0.10 micrograms/10(7) cells. In S37-bearing mice, Pro 23.3, 46.6, and 116.5 micrograms.ml-1 enhanced the malondialdehyde (MDA) formation in tumor and liver mitochondria and decreased MDA formation in liver mitochondria. These results suggested that the increases of Dox accumulation and MDA formation in tumor cells by Pro might be the reasons for synergistic effect of Pro on Dox cytotoxicity.
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PMID:Synergistic effect of probimane on anticancer cytotoxicity of doxorubicin in vitro. 801 87


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