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PMID:9041188 | Nine human ovarian cancer cell lines that express wild-type (wt) or mutated p53 were used to evaluate the cytotoxicity induced by paclitaxel. | [
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PMID:9041188 | The IC50 calculated in the five mutated p53-expressing cell lines was not different from the four wt p53-expressing cell lines. | [
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PMID:9041188 | The introduction of wt p53, by using a temperature-sensitive mutant murine p53 or the human p53 under the control of a tetracycline-dependent promoter, did not change the cytotoxicity of paclitaxel as compared to mock-transfected cells. | [
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PMID:9041188 | By using for each cell line the paclitaxel IC50, we found that these concentrations were sufficient to induce an increase in p53 levels in all of the four wt p53-expressing cells, whereas in the mutated p53-expressing cells, the levels were unaffected. | [
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PMID:9041188 | This increase in p53 levels led to an increase in the mRNA and protein levels of p53 downstream genes (WAF1, GADD45, and bax). | [
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] |
PMID:9041188 | In none of the cell lines examined was paclitaxel able to induce apoptosis, evaluated by terminal deoxynucleotidyl transferase-mediated nick end labeling staining and filter binding assay at concentrations closed to the IC50. | [
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] |
PMID:9041188 | By increasing the concentration of paclitaxel in the filter binding assay, we could see fragmentation of DNA in the different cell lines. | [
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PMID:9041188 | We conclude that the presence of p53 is not a determinant for the cytotoxicity induced by paclitaxel in human ovarian cancer cell lines. | [
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PMID:9041188 | Differences in the activation of p53 downstream genes could be observed in wt versus mutated p53-expressing cells, but this does not account either for a differential induction of apoptosis or for a change in cytotoxicity induced by paclitaxel. | [
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PMID:14991574 | Sulfamoylation of 2-methoxyestrone (2-MeOE1) was shown previously to enhance its potency as an anti-proliferative agent against breast cancer cells. | [
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PMID:14991574 | We have examined the ability of a series of 2-methoxyestradiol (2-MeOE2) and 2-ethylestradiol (2-EtE2) sulfamates to inhibit angiogenesis in vitro. | [
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] |
PMID:14991574 | 2-MeOE2 bis-sulfamate and 2-EtE2 sulfamate were potent inhibitors of human umbilical vein endothelial cell (HUVEC) proliferation with IC(50) values of 0.05 microM and 0.01 microM, respectively. | [
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PMID:14991574 | A novel co-culture system, in which endothelial cells were cultured in a matrix of human dermal fibroblasts, was also used to assess the anti-angiogenic potential of these drugs. | [
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PMID:14991574 | In this system endothelial cells proliferate and migrate through the culture matrix to form tubule structures. | [
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PMID:14991574 | Whereas 2-MeOE2 (1.0 microM) caused a small reduction in tubule formation, both 2-MeOE2 bis-sulfamate (0.1 microM) and 2-EtE2 sulfamate (0.1 microM) almost completely abolished tubule formation. | [
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PMID:14991574 | 2-MeOE2 bis-sulfamate and 2-EtE2 sulfamate both induced BCL-2 phosphorylation, p53 protein expression and apoptosis in HUVECs. | [
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PMID:14991574 | Microarray analysis of a limited number of genes known to be involved in the angiogenic process did not show any gross changes in cells treated with the 2-substituted estrogens. | [
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PMID:14991574 | The sulfamoylated derivatives of 2-MeOE2 and 2-EtE2 are potent inhibitors of in vitro angiogenesis and both compounds should have therapeutic potential. | [
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PMID:15990222 | Treatment failures result from resistance to chemotherapy in ovarian cancer. | [
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] |
PMID:15990222 | The effect of cisplatin and paclitaxel treatments on chemosensitivity was studied in ovarian cancer cells developed from a patient with stage IIIC disease. | [
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PMID:15990222 | Cells (UL-3A, UL-3B) that recovered from cisplatin (Cis) and paclitaxel (Tax) treatments showed higher levels of p53, mdr-1 and chemoresistance than untreated controls. | [
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PMID:15990222 | EC50 values of Cis and Tax for UL-3A clones were 7.2-34.6, average 20.9 microg/ml, while UL-3B clones ranged from 11.8-252.0 microg/ml, with a mean value of 73.2 microg/ml for Cis, and 260.0-4400.0 nM (mean 2555.0 nM) for Tax. | [
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PMID:15990222 | Selection pressures during treatment may contribute to drug resistance. | [
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PMID:9231689 | Tumors are thought to differ in their response to cytotoxic agents for a variety of reasons including cell cycle kinetics, degree of hypoxia, differential repair, and ability to survive when stressed. | [
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PMID:9231689 | Our previous studies showed that murine mammary carcinoma MCA-4 tumors are relatively sensitive to both radiation and paclitaxel and exhibit a significant apoptotic response following treatment in vivo. | [
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PMID:9231689 | In contrast, murine squamous cell carcinoma SCC-VII tumors are relatively resistant to radiation and paclitaxel and exhibit relatively little apoptosis following treatment. | [
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PMID:9231689 | Since dysfunctional p53 has been shown to be associated with tumor resistance, perhaps through a dysregulated cell loss mechanism, we examined the role of p53 expression in the differential apoptotic response of these two tumors following cytotoxic treatment in vivo. | [
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PMID:9231689 | Mice bearing 8-mm tumors were treated with 40 mg/kg paclitaxel i.v. | [
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PMID:9231689 | or 15 Gy local tumor irradiation, and tumors were harvested at several time points up to 2 days following treatment. | [
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PMID:9231689 | Histological sections of the tumors were then assessed micromorphometrically for mitotic arrest and apoptosis and immunohistochemically for p53 and p21 expression. | [
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PMID:9231689 | In the apoptosis-sensitive MCA-4 tumors, p53 expression increased rapidly following radiation from 13% at baseline to a peak of 45% within 3 h, and expression remained elevated for more than 24 h. Radiation also upregulated p21 suggesting that radiation-induced apoptosis in MCA-4 tumor is p53 dependent. | [
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PMID:9231689 | Paclitaxel also induced an increase in both p53 and p21 expression in MCA-4 cells; however, the increase was delayed compared to that after irradiation. | [
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PMID:9231689 | This upregulation occurred after the onset of apoptosis which would suggest that paclitaxel-induced apoptosis is p53 independent. | [
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PMID:9231689 | Both radiation and paclitaxel caused p53 upregulation in the apoptosis-resistant SCC-VII tumors. | [
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PMID:9231689 | The untreated SCC-VII tumor has 25% cells p53 positive and has a very high level of p21 (87% cells positive) which suggests a downstream defect in p53 response. | [
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] |
PMID:9231689 | These results show that tumor responsiveness to paclitaxel and radiation, measured by tumor growth delay, was associated with apoptotic response. | [
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] |
PMID:9231689 | However, although both agents upregulated p53 expression in these tumors, the association between this upregulation and induction of apoptosis was not clear. | [
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] |
PMID:9231689 | Additional studies using these and other tumors are warranted to elucidate the role of p53 and its downstream effectors in the in vivo responsiveness of tumors to paclitaxel and radiation. | [
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PMID:16601104 | Non-small cell lung cancer (NSCLC) demonstrates a strong etiologic association with smoking. | [
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PMID:16601104 | Although nicotine is not carcinogenic, it can induce cell proliferation and angiogenesis and suppress apoptosis induced by certain agents. | [
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PMID:16601104 | Here we show that nicotine inhibits apoptosis induced by the drugs gemcitabine, cisplatin, and taxol, which are used to treat NSCLCs. | [
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PMID:16601104 | This protection correlated with the induction of XIAP and survivin by nicotine in a panel of human NSCLC cell lines, and depletion of XIAP and survivin ablated the protective effects of nicotine. | [
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PMID:16601104 | The antiapoptotic effects of nicotine were mediated by dihydro beta-erythroidine-sensitive alpha3-containing nicotinic acetylcholine receptors and required the Akt pathway. | [
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PMID:16601104 | Chromatin immunoprecipitation assays demonstrated that nicotine stimulation caused an increased recruitment of E2F1 and concomitant dissociation of retinoblastoma tumor suppressor protein (Rb) from survivin promoter in A549 cells. | [
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PMID:16601104 | Moreover, ablation of E2F1 levels caused abrogation of the protective effects of nicotine against cisplatin-induced apoptosis in A549 cells whereas ablation of signal transducer and activator of transcription 3 levels had no effect. | [
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PMID:16601104 | These studies suggest that exposure to nicotine might negatively impact the apoptotic potential of chemotherapeutic drugs and that survivin and XIAP play a key role in the antiapoptotic activity of nicotine. | [
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PMID:16413505 | Recent data showed that epidermal growth factor receptor (EGFR) inhibitors, such as ZD1839, alone or in combination with chemotherapeutic agents for androgen-independent prostate cancer (AIPC) did not produce promising results in clinical settings. | [
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PMID:16413505 | More effective regimens involving novel stronger inhibitor of EGFR and better combinations are needed. | [
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PMID:16413505 | The anti-tumor activity of PD168393, an irreversible EGFR inhibitor, with or without chemotherapeutic agents for the treatment of AIPC was investigated in vitro. | [
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] |
PMID:16413505 | In results, both the androgen-independent cell lines PC-3 and DU145 expressed higher levels of EGFR than the androgen-dependent MDA PCa 2b and androgen-responsive LNCaP cells by Western blotting. | [
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PMID:16413505 | DU145 was much more sensitive to PD168393 and ZD1839 than MDA PCa 2b. | [
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PMID:16413505 | PD168393, but not ZD1839, significantly potentiated paclitaxel cytotoxicity against DU145 by MTT assay and median-effect analysis. | [
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] |
PMID:16413505 | The combination of PD168393 or ZD1839 with other cytotoxic agents including docetaxel and 5-fluorouracil, however, was either additive or antagonistic. | [
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PMID:16413505 | Compared to paclitaxel alone, PD168393 significantly enhanced paclitaxel-induced DNA fragmentation, sub-G1 fraction accumulation, mitochondrial membrane dysfunction, cytochrome C release, caspase-3 activation and eventually apoptosis. | [
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] |
PMID:16413505 | These molecular events were accompanied by Bad up-regulation, p53 and p21Waf1/Cip1 induction, ERK1/2 inactivation and inhibition of EGFR phosphorylation in the presence of PD168393. | [
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PMID:16413505 | These effects did not involve significant alteration in the Akt1/2 and STAT3 signaling pathway. | [
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PMID:16413505 | In conclusion, the combination of paclitaxel and PD168393 produced a profound synergistic growth inhibition of AIPC cells. | [
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] |
PMID:16413505 | Combining PD168393 with paclitaxel may have clinical benefits and warrants further investigation. | [
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PMID:12082016 | Human Tp53 is normally a short-lived protein. | [
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PMID:12082016 | Tp53 protein is stabilized and levels are increased in response to a variety of cellular stresses, including those induced by genotoxic anticancer drugs and environmental exposures. | [
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] |
PMID:12082016 | To engineer an efficient assay based on this property, we constructed and integrated a Tp53-specific reporter system into human cancer cells, termed p53R cells. | [
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PMID:12082016 | We tested a range of conventional chemotherapeutic agents as well as over 16 000 diverse small compounds. | [
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] |
PMID:12082016 | Ionizing radiation and two-thirds of conventional chemotherapeutic agents, but only 0.2% of diverse compounds activated Tp53 activity by two-fold or greater, consistent with the presumptive genotoxic activation of Tp53 function. | [
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PMID:12082016 | Cytotoxicity was independent of TP53 genetic status when paired, syngeneic wild-type TP53 and TP53-null cells in culture were treated with compounds that activated Tp53. | [
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PMID:12082016 | From the unbiased survey of random compounds, Tp53 activation was strongly induced by an analog of AMSA, an investigational anti-cancer agent. | [
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PMID:12082016 | Tp53 was also strongly induced by an N-oxide of quinoline and by dabequine, an experimental antimalarial evaluated in humans; dabequine was reported to be negative in other screens of mutagenicity and clastogenicity but carcinogenic in animal studies. | [
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PMID:12082016 | Further exploration of antimalarial compounds identified the common medicinals chloroquine, quinacrine, and amodiaquine as Tp53-inducers. | [
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] |
PMID:12082016 | Flavonoids are known to have DNA topoisomerase activity, a Tp53-inducing activity that is confirmed in the assay. | [
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PMID:12082016 | A reported clinical association of Tp53 immunopositive colorectal cancers with use of the antihypertensive agents was extended by the demonstration of hydralazine and nifedipine as Tp53-inducers. | [
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PMID:12082016 | p53R cells represent an efficient Tp53 functional assay to identify chemicals and other agents with interesting biologic properties, including genotoxicity. | [
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] |
PMID:12082016 | This assay may have utility in the identification of novel chemotherapeutic agents, as an adjunct in the pharmaceutical optimization of lead compounds, in the exploration of environmental exposures, and in chemical probing of the Tp53 pathway. | [
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PMID:16168113 | The aim of the study was to evaluate the activity of a combination of doxorubicin (Dox), paclitaxel (Pacl) and 5-fluorouracil (5-FU), to define the most effective schedule, and to investigate the mechanisms of action in human breast cancer cells. | [
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PMID:16168113 | The study was performed on MCF-7 and BRC-230 cell lines. | [
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PMID:16168113 | The cytotoxic activity was evaluated by sulphorhodamine B assay and the type of drug interaction was assessed by the median effect principle. | [
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PMID:16168113 | Cell cycle perturbation and apoptosis were evaluated by flow cytometry, and apoptosis-related marker (p53, bcl-2, bax, p21), caspase and thymidylate synthase (TS) expression were assessed by western blot. | [
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] |
PMID:16168113 | 5-FU, used as a single agent, exerted a low cytotoxic activity in both cell lines. | [
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PMID:16168113 | The Dox-->Pacl sequence produced a synergistic cytocidal effect and enhanced the efficacy of subsequent exposure to 5-FU in both cell lines. | [
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PMID:16168113 | Specifically, the Dox-->Pacl sequence blocked cells in the G2-M phase, and the addition of 5-FU forced the cells to progress through the cell cycle or killed them. | [
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PMID:16168113 | Furthermore, Dox-->Pacl pretreatment produced a significant reduction in basal TS expression in both cell lines, probably favoring the increase in 5-FU activity. | [
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PMID:16168113 | The sequence Dox-->Pacl-->48-h washout-->5-FU produced a synergistic and highly schedule-dependent interaction (combination index < 1), resulting in an induction of apoptosis in both experimental models regardless of hormonal, p53, bcl-2 or bax status. | [
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PMID:16168113 | Apoptosis in MCF-7 cells was induced through caspase-9 activation and anti-apoptosis-inducing factor hyperexpression. | [
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PMID:16168113 | In the BRC-230 cell line, the apoptotic process was triggered only by a caspase-dependent mechanism. | [
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PMID:16168113 | In particular, at the end of the three-drug treatment, caspase-8 activation triggered downstream executioner caspase-3 and, to a lesser degree, caspase-7. | [
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] |
PMID:16168113 | In our experimental models, characterized by different biomolecular profiles representing the different biology of human breast cancers, the schedule Dox-->Pacl-->48-h washout-->5-FU was highly active and schedule-dependent and has recently been used to plan a phase I/II clinical protocol. | [
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PMID:11774260 | Paclitaxel exerts its cytotoxic effect by kinetic suppression of microtubules that block cells in the G2/M phase of the cell cycle and trigger apoptosis. | [
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] |
PMID:11774260 | To investigate apoptosis induced by paclitaxel in nasopharyngeal carcinoma (NPC), and its possible molecular mechanism of action, the human NPC cell lines HNE-1 (bearing wild-type p53) and CNE-2 (bearing mutant p53) were treated with different concentrations of paclitaxel. | [
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PMID:11774260 | Apoptosis was determined by staining with propidium iodide and also by DNA fragmentation. | [
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PMID:11774260 | Protein expression levels of p53, bcl-2 and bcl-xl were examined by Western blotting. | [
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] |
PMID:11774260 | Activation of caspase-3 and cleavage of poly(ADP-ribose) polymerase (PARP) were also studied in paclitaxel-induced apoptosis. | [
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PMID:11774260 | We showed that paclitaxel inhibited growth and induced apoptosis in both cell lines but that the p53 mutant line (CNE-2) was less sensitive to treatment with low-dose paclitaxel. | [
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PMID:11774260 | Caspase-3 activity and cleavage of death substrate PARP were significantly increased in a dose-dependent manner, both in parallel with the induction of apoptosis and growth inhibition of NPC cells. | [
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] |
PMID:11774260 | We observed a striking increase of p53 protein levels in NPC cells exposed to 1 and 10 nM paclitaxel but a marked inhibition at 100 nM paclitaxel treatment. | [
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PMID:11774260 | An inhibitor of caspase, zVAD.fmk, blocked the apoptotic morphologic changes and DNA fragmentation but did not change the rate of cell death or the protein levels of p53, bcl-2 and bcl-xl. | [
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] |
PMID:11774260 | In summary, low-dose paclitaxel inhibited cell growth in NPC cells and induced apoptosis possibly by upregulation of p53. | [
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PMID:11774260 | In contrast, cell growth and apoptosis induced by a high dose of the drug occurred in a p53-independent manner, which may directly initiate downstream events of apoptosis. | [
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PMID:33002289 | Despite advances in treatment, breast cancer remains the widest spread disease among females with a high mortality rate. | [
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PMID:33002289 | We investigated the potential effects of gallic acid (GA) as supportive therapy in the management of breast cancer. | [
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PMID:33002289 | Anti-cancer activity with GA alone or in combination with paclitaxel and/or carboplatin was assessed by MTT assay and flow cytometry using annexin V/propidium iodide. | [
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] |
PMID:33002289 | The mechanism underlying the antiproliferative effects was investigated by measuring the expression of the pro-apoptotic marker (Bax), CASP-3, anti-apoptotic (Bcl-2), and, tumor suppressor (p53) by real-time polymerase chain reaction (RT-PCR) and western blot analysis. | [
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PMID:33002289 | Cell cycle analysis was performed for the MCF-7 breast cancer cell line. | [
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Subsets and Splits