Cytotoxic studies of paclitaxel (Taxol®) in human tumour cell lines

Liebmann, James; Cook, John A.; Lipschultz, Claudia A.; Teague, Diane; Fisher, Joyce M.; Mitchell, James B.

doi:10.1038/bjc.1993.488

Cited by 368 publications

(228 citation statements)

References 14 publications

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“…The duration of drug exposure was longer for paclitaxel cytotoxic e ect than for p21 induction or cell cycle e ect. Indeed, it has been shown that increasing the time of exposure to paclitaxel results in a marked increase in cytotoxicity (Liebmann et al, 1993). According to this author, we found that a similar dose of paclitaxel (1 nM) induced a cytotoxic e ect which depends on the duration of paclitaxel treatment.…”

Section: In¯uence Of Antisense-p21 On Cell Survival After Paclitaxel supporting

confidence: 54%

Involvement of p21 in mitotic exit after paclitaxel treatment in MCF-7 breast adenocarcinoma cell line

et al. 1997

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It has been shown recently that expression of p21 is enhanced by paclitaxel. This cytotoxic compound induces mitotic spindle damage resulting in blockade of the mitotic cell cycle associated or not with apoptotic cell death. In the present study, we showed that, in MCF-7 cells, paclitaxel induced accumulation of p21 in cells with a G2/M DNA content, corresponding to cells either in abnormal mitosis or in an interphase-like state (decondensed chromatin) with multiple nuclei. In MCF-7 cells, the increase in p21 was subsequent to the mitotic arrest and was associated with the exit from abnormal mitosis leading to formation of cells with micronuclei. In this cell line, we noted a relationship between the elevation of p21 expression and the inhibition of p34 cdc2 activity. High levels of p21 protein were also found to be associated with inactive p34 cdc2 /cyclin B protein complex after treatment with paclitaxel. Treatment with p21 antisense oligonucleotide partially blocked induction of p21 expression by paclitaxel and signi®cantly reduced survival of MCF-7 cells exposed to this agent. In NIH-OVCAR-3 cells, which are de®cient in basal and paclitaxel-induced p21 expression, paclitaxel led to a prolonged activation of p34 cdc2 and a delayed mitotic exit associated with apoptotic cell death. These observations suggest that p21 is not required for the mitotic arrest in response to paclitaxel, but argue in favor of a role for this inhibitor in facilitating the exit from abnormal mitosis. This e ectively enhances cell survival after paclitaxel-induced spindle damage.

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Section: In¯uence Of Antisense-p21 On Cell Survival After Paclitaxel supporting

confidence: 54%

Involvement of p21 in mitotic exit after paclitaxel treatment in MCF-7 breast adenocarcinoma cell line

et al. 1997

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“…This indicates that the cellular effects as shown in our three-dimensional assays were not caused by any interference with the paclitaxel solvent. These observations may contradict other findings showing cytotoxic effects of Cremophor EL on tumour cells (Liebmann et al, 1993;Nygren et al, 1995). However, the results that were obtained in these studies were based on experiments performed on monolayer cell cultures.…”

Section: Discussionmentioning

confidence: 60%

Proliferation, migration and invasion of human glioma cells exposed to paclitaxel (Taxol) in vitro

Terzis

Thorsen²,

Heese³

et al. 1997

Br J Cancer

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Summary Paclitaxel (Taxol), an anti-cancer drug derived from Taxus species, was tested for its anti-migrational, anti-invasive and antiproliferative effect on two human glioma cell lines (GaMg and D-54Mg) grown as multicellular tumour spheroids. In addition, the direct effect of paclitaxel on glioma cells was studied using flow cytometry and scanning confocal microscopy. Both cell lines showed a dose-dependent growth and migratory response to paclitaxel. The GaMg cells were found to be 5-10 times more sensitive to paclitaxel than D-54Mg cells. Paclitaxel also proved to be remarkably effective in preventing invasion in a co-culture system in which tumour spheroids were confronted with fetal rat brain cell aggregates. Control experiments with Cremophor EL (the solvent of paclitaxel for clinical use) in this study showed no effect on tumour cell migration, cell proliferation or cell invasion. Scanning confocal microscopy of both cell lines showed an extensive random organization of the microtubules in the cytoplasm. After paclitaxel exposure, the GaMg and the D-54Mg cells exhibited a fragmentation of the nuclear material, indicating a possible induction of apoptosis. In line with this, flow cytometric DNA histograms showed an accumulation of cells in the G/M phase of the cell cycle after 24 h of paclitaxel exposure. After 48 h, a deterioration of the DNA histograms was observed indicating nuclear fragmentation.

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“…These assays were performed according to the protocol of Liebmann et al (1993) with some modifications. Petri dishes (100 mm) (Corning, High Wycombe, UK) were plated with 5 Â 10 5 cells in 10 ml of media or 60-mm Petri dishes were plated with 1.8 Â 10 5 cells in 3.5 ml of media.…”

Section: Assaysmentioning

confidence: 99%

Cytotoxic and antiangiogenic activity of AW464 (NSC 706704), a novel thioredoxin inhibitor: an in vitro study

et al. 2005

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AW464 (NSC 706704) is a novel benzothiazole substituted quinol compound active against colon, renal and certain breast cancer cell lines. NCI COMPARE analysis indicates possible interaction with thioredoxin/thioredoxin reductase, which is upregulated under hypoxia. Through activity on HIF1a, VEGF levels are regulated and angiogenesis controlled. A thioredoxin inhibitor could therefore exhibit enhanced hypoxic toxicity and indirect antiangiogenic effects. In vitro experiments were performed on colorectal and breast cancer cell lines under both normoxic and hypoxic conditions and results compared against those obtained with normal cell lines, fibroblasts and keratinocytes. Antiangiogenic effects were studied using both large and microvessel cells. Indirect antiangiogenic effects (production of angiogenic growth factors) were studied via ELISA. We show that AW464 exerts antiproliferative effects on tumour cell lines as well as endothelial cells with an IC 50 of B0.5 mM. Fibroblasts are however resistant. Proliferating, rather than quiescent, endothelial cells are sensitive to the drug indicating potential antiangiogenic rather than antivascular action. Endothelial differentiation is also inhibited in vitro. Hypoxia (1% O 2 for 48 h) sensitises colorectal cells to lower drug concentrations, and in HT29s greater inhibition of VEGF is observed under such conditions. In contrast, bFGF levels are unaffected, suggesting possible involvement of HIF1a. Thus, AW464 is a promising chemotherapeutic drug that may have enhanced potency under hypoxic conditions and also additional antiangiogenic activity.

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Cytotoxic studies of paclitaxel (Taxol®) in human tumour cell lines

Cited by 368 publications

References 14 publications

Involvement of p21 in mitotic exit after paclitaxel treatment in MCF-7 breast adenocarcinoma cell line

Involvement of p21 in mitotic exit after paclitaxel treatment in MCF-7 breast adenocarcinoma cell line

Proliferation, migration and invasion of human glioma cells exposed to paclitaxel (Taxol) in vitro

Cytotoxic and antiangiogenic activity of AW464 (NSC 706704), a novel thioredoxin inhibitor: an in vitro study

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