Microtubule Dysfunction Induced by Paclitaxel Initiates Apoptosis through Both c-Jun N-terminal Kinase (JNK)-dependent and -Independent Pathways in Ovarian Cancer Cells

Wang, Tzu‐Hao; Popp, Diana M.; Wang, Hsin-Shih; Saitoh, Masao; Mural, J.G.; Henley, Donald C.; Ichijo, Hidenori; Wimalasena, Jay

doi:10.1074/jbc.274.12.8208

Cited by 194 publications

(155 citation statements)

References 61 publications

Supporting

Mentioning

142

Contrasting

Order By: Relevance

“…inhibited the phosphorylation of c-Jun by paclitaxel-activated c-Jun N-terminal kinase Consistent with the results of previous studies (Wang et al, 1999(Wang et al, , 1998, a 2-h treatment of paclitaxel at concentrations that ranged from 0.1 to 10 mM activated JNK in BR ovarian cancer cells. This can be seen by the phosphorylation of JNK (Figure 1a,upper panel).…”

Section: Sp600125supporting

confidence: 90%

“…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%

“…The paclitaxel-activated JNK signaling pathway has been correlated with tumor cell death in many types of ovarian cancer (Lee et al, 1996;Wang et al, 1999Wang et al, , 1998MacKeigan et al, 2000), breast cancer (Wang et al, 1998;MacKeigan et al, 2000) and lung cancer (MacKeigan et al, 2000), suggesting that it may be a common mechanism of chemotherapy. Using DNA microarray (from 4 to 1625 pg/1000 cells in 24 h, as specified in parentheses) IL-6 into culture media.…”

Section: Discussionmentioning

confidence: 99%

“…Human ovarian cancer cell line BR cells were cultured in DMEM-F12 medium with 10% fetal bovine serum, penicillin (100 U/ml) and streptomycin (100 U/ml), at 371C in a 5% CO 2 atmosphere as described previously (Wang et al, 1998(Wang et al, , 1999. Additional seven ovarian cancer cell lines, Caov3, MDAH 2774, SKOV-3, TOV-21G, TOV-112D, OV-90 and OVCAR-3, were obtained from the ATCC (Rockville, MD, USA).…”

Section: Cell Culture and Treatmentmentioning

confidence: 99%

“…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%

See 4 more Smart Citations

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

Chan

Chen

et al. 2006

Oncogene

View full text Add to dashboard Cite

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.

show abstract

Section: Sp600125supporting

confidence: 90%

Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Section: Cell Culture and Treatmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Chan

Chen

et al. 2006

Oncogene

View full text Add to dashboard Cite

show abstract

Methylglyoxal induces apoptosis in Jurkat leukemia T cells by activating c-Jun N-Terminal kinase

et al. 2000

View full text Add to dashboard Cite

Methylglyoxal (MG) is a physiological metabolite, but it is known to be toxic, inducing stress in cells and causing apoptosis. This study examines molecular mechanisms in the MG-induced signal transduction leading to apoptosis, focusing particularly on the role of JNK activation. We first confirmed that MG caused apoptosis in Jurkat cells and that it was cell type dependent because it failed to induce apoptosis in MOLT-4, HeLa, or COS-7 cells. A caspase inhibitor, Z-DEVD-fmk, completely blocked MG-induced poly(ADP-ribose)polymerase (PARP) cleavage and apoptosis, showing the critical role of caspase activation. Inhibition of JNK activity by a JNK inhibitor, curcumin, remarkably reduced MG-induced caspase-3 activation, PARP cleavage, and apoptosis. Stable expression of the dominant negative mutant of JNK also protected cells against apoptosis notably, although not completely. Correspondingly, loss of the mitochondrial membrane potential induced by MG was decreased by the dominant negative JNK. These results confirmed a crucial role of JNK working upstream of caspases, as well as an involvement of JNK in affecting the mitochondrial membrane potential.

show abstract

Paclitaxel-induced cell death

Wang

Soong

2000

Cancer

Self Cite

562

201

View full text Add to dashboard Cite

Microtubule Dysfunction Induced by Paclitaxel Initiates Apoptosis through Both c-Jun N-terminal Kinase (JNK)-dependent and -Independent Pathways in Ovarian Cancer Cells

Cited by 194 publications

References 61 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

Methylglyoxal induces apoptosis in Jurkat leukemia T cells by activating c-Jun N-Terminal kinase

Paclitaxel-induced cell death

Contact Info

Product

Resources

About