Paclitaxel-induced cell death

Wang, Tzu‐Hao; Wang, Hsin-Shih; Soong, Yung Kuei

doi:10.1002/1097-0142(20000601)88:11<2619::aid-cncr26>3.0.co;2-j

Cited by 552 publications

(200 citation statements)

References 91 publications

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“…Our previous studies reinforced this conclusion (Wang et al, 1999(Wang et al, , 1998(Wang et al, , 2000. Results of this study demonstrated that paclitaxel in this range of concentrations activated IL-6 through the activation of JNK signaling pathway but not through the LPS-like activity of paclitaxel.…”

Section: Discussionsupporting

confidence: 79%

“…In addition to its stabilizing effects on the microtubules and the subsequent cell cycle arrest in the G2-M phase, paclitaxel also induces the vast activation of signal-transduction pathways that may be associated with proapoptotic signaling (Blagosklonny and Fojo, 1999;Taxman et al, 2003). Among the proapoptotic signaling networks activated by paclitaxel (Meikrantz and Schlegel, 1996;Lee et al, 1997), the c-Jun Nterminal kinase (JNK) signaling pathway played an important role (Lee et al, 1998;Wang et al, 1999Wang et al, , 2000MacKeigan et al, 2000;Vivat-Hannah et al, 2001;Mingo-Sion et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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Paclitaxel (Taxol) upregulates expression of functional interleukin-6 in human ovarian cancer cells through multiple signaling pathways

Chan

Chen

et al. 2006

Oncogene

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Paclitaxel (Taxol) is an antineoplastic agent that specifically targets microtubules and arrests cells at the G2/M phase of the cell cycle. In addition to mitotic arrest, the activation of c-Jun N-terminal kinase (JNK) signaling pathway has been demonstrated to be involved in the process leading to apoptosis. In an attempt to explore what genes are transcriptionally regulated by the activated JNK signaling pathway upon paclitaxel treatment, we used cDNA microarrays to analyse the changes of gene expression in human ovarian cancer cells that were treated with paclitaxel and/or the JNK inhibitor SP600125. Among 20 genes that were specifically regulated by the paclitaxel-activated JNK pathway, interleukin (IL)-6 was shown to elicit function through the JAK-STAT signaling pathway in an autocrine and/or paracrine fashion. Subsequently, we identified that 87.5% of eight tested ovarian cancer lines secreted detectable levels of IL-6, which could be further upregulated 2-3.2 fold by 1 lM paclitaxel. Dissection on regulatory pathways for IL-6 indicated that (i) when ovarian cancer cells were treated with paclitaxel at low but clinically achievable concentrations (exemplified by 1 lM in this study), the JNK signaling pathway was the major stimulator of IL-6 gene regulation and (ii) at suprapharmacologically high concentrations (exemplified by 50 lM), paclitaxel exerted lipopolysaccharide-like effects, most likely through the Toll-like receptor 4 signaling pathway. Collectively, these results suggest that paclitaxel upregulates functional IL-6 expression in human ovarian cancer cells through multiple signaling pathways.

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Section: Discussionsupporting

confidence: 79%

Section: Introductionmentioning

confidence: 99%

Paclitaxel (Taxol) upregulates expression of functional interleukin-6 in human ovarian cancer cells through multiple signaling pathways

Chan

Chen

et al. 2006

Oncogene

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“…The stimuli reported to induce JNK-dependent cell death are stress inducers such as UV-and g-irradiation (Chen et al, 1996;Zanke et al, 1996;Butterfield et al, 1997;Tournier et al, 2000) as well as cytotoxic drugs (Chen et al, 1999;Shiah et al, 1999Shiah et al, , 2001Watabe et al, 1999;Eichhorst et al, 2000;Mandlekar et al, 2000;SanchezPerez et al, 2000;Wang et al, 2000) and anticarcinogenic compounds such as isothiocyanates (Chen et al, 1998). Thus, JNK has been suggested to be required for stress-induced mitochondrial death signaling pathways (Tournier et al, 2000).…”

Section: Role Of Jnk In Ajoene-induced Apoptotic Signalingmentioning

confidence: 99%

Ajoene-induced cell death in human promyeloleukemic cells does not require JNK but is amplified by the inhibition of ERK

et al. 2003

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Treatment of human promyeloleukemic HL-60 cells with the experimental antileukemic drug ajoene induces the activation of the mitogen-activated protein kinases (MAPKs) c-Jun NH 2 -terminal kinase (JNK), p38 and extracellular signal-regulated kinases (ERK) 1/2 as well as the survival kinase Akt. JNK activation occurred in HL-60/neo, HL-60/bcl-x L , and in HL-60 cells pretreated with the pan-caspase inhibitor zVAD-fmk, indicating that JNK activation is not dependent on ajoene-induced mitochondria perturbation and subsequent caspase activation. Cells overexpressing a dominant-negative JNK showed no altered sensitivity towards ajoene suggesting that the activation of JNK is not necessary for ajoeneinduced cell death. Inhibition of p38 MAPK by SB 203580 had no influence on ajoene-mediated apoptosis. In contrast, inhibition of ERK1/2 vastly enhanced ajoeneinduced cell death. The survival kinase Akt, in contrast, did not participate in ajoene-induced death signaling as shown by the use of the phosphatidylinositol-3-kinase inhibitor wortmannin. Thus in contrast to the previous findings regarding stress-induced cell death, ajoenemediated activation of JNK and p38 has no impact on ajoene-induced apoptosis in HL-60 cells. Blockade of ERK1/2 but not Akt pathways leads to sensitization of cells against ajoene-mediated apoptosis supporting the view that inhibition of ERK1/2 is a valuable strategy to increase the sensitivity of promyeloleukemic cells towards ajoene.

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“…PTX stabilizes microtubules, which interferes with the formation of the mitotic spindle, inducing a mitotic block (Jordan et al, 1993). The cytotoxic effects of PTX have been linked to its inhibition of microtubule function (Mollinedo and Gajate, 2003) and the upregulation of the proapoptotic proteins, Bax (Srivastava et al, 1998) and Bak (Wang et al, 2000) and the downregulation and inactivation of the antiapoptotic protein, Bcl-2 (Wang et al, 2000;Ferlini et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Paclitaxel induces the phosphorylation of the eukaryotic translation initiation factor 4E-binding protein 1 through a Cdk1-dependent mechanism

Greenberg

Zimmer

2005

Oncogene

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Initial chemotherapeutic treatment triggers a stressrelated response, which can lead to an increase in the expression of survival proteins. In this study we examine whether paclitaxel (PTX) alters the expression and/or phosphorylation of the translation initiation proteins, eukaryotic initiation factor 4E (eIF-4E) and 4E-binding protein (4E-BP1), a suppressor of eIF-4E in the dephosphorylated state. We found that PTX induced the hyperphosphorylation of 4E-BP1 in the breast cancer cell line, MDA MB 231, which reduced its association with eIF-4E, but did not alter the expression and phosphorylation of eIF-4E. The hyperphosphorylation of 4E-BP1 correlated with G2/M accumulation and with an increase in the phosphorylation of cdk1 substrates. Cotreatment with a histone deacetylase inhibitor (an indirect inhibitor of cdk activity), purvalanol A and roscovitine (direct cdk inhibitors), and the reduction of cyclin B expression using RNA interference decreased the hyperphosphorylation of 4E-BP1 in PTX treated cells. The hyperphosphorylation of 4E-BP1 by PTX increased the association of eIF-4E with eIF-4G, whereas cotreatment with purvalanol A inhibited the association of eIF-4E with eIF-4G in PTX treated cells. Taken together, our data suggest that PTXincreases the functional level of eIF-4E by promoting the hyperphosphorylation and release of 4E-BP1 through a cdk1-dependent mechanism.

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Paclitaxel-induced cell death

Cited by 552 publications

References 91 publications

Paclitaxel (Taxol) upregulates expression of functional interleukin-6 in human ovarian cancer cells through multiple signaling pathways

Paclitaxel (Taxol) upregulates expression of functional interleukin-6 in human ovarian cancer cells through multiple signaling pathways

Ajoene-induced cell death in human promyeloleukemic cells does not require JNK but is amplified by the inhibition of ERK

Paclitaxel induces the phosphorylation of the eukaryotic translation initiation factor 4E-binding protein 1 through a Cdk1-dependent mechanism

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