Inhibition of Phosphorylation of BAD and Raf-1 by Akt Sensitizes Human Ovarian Cancer Cells to Paclitaxel

Mabuchi, Seiji; Ohmichi, Masahide; Kimura, Akiko; Hisamoto, Koji; Hayakawa, Jun; Nishio, Yukihiro; Adachi, K.; Takahashi, Kazuhiro; Arimoto-Ishida, Emi; Nakatsuji, Yuki; Tasaka, Keiichi; Murata, Yuji

doi:10.1074/jbc.m204042200

Cited by 162 publications

(141 citation statements)

References 65 publications

Supporting

Mentioning

132

Contrasting

Unclassified

Order By: Relevance

“…Collectively, these results indicate that paclitaxel transiently induces phosphorylation of IKK and I B␣ as well as activation of NF B via a PI3K/Akt cascade, followed by the decrease in NF B activity thereafter. As we reported previously (11), similar findings were also detected in other ovarian cancer cell lines (data not shown). We first confirmed that treatment with BAY 11-7085 attenuated both basal and transient induction of I B␣ phosphorylation by paclitaxel (Fig.…”

Section: Resultssupporting

confidence: 92%

“…We reported that Akt inactivation and inhibition of BAD phosphorylation sensitize human ovarian cancer cells to cisplatin (10) and paclitaxel (11). In addition, we showed recently that inhibition of Forkhead phosphorylation sensitizes human ovarian cancer cells to cisplatin (50).…”

Section: Discussionmentioning

confidence: 98%

“…Therefore, it is possible that antiapoptotic signals such as the phosphatidylinositol 3-kinase (PI3K)/ Akt survival cascade are involved in the sensitivity to chemotherapeutic drugs. We reported that Akt inactivation sensitizes human ovarian cancer cells to cisplatin (10) and paclitaxel (11), suggesting that Akt inactivation could be a hallmark of the sensitivity of cells to some chemotherapeutic drugs. Possible mechanisms by which Akt promotes cell survival include phosphorylation and inactivation of the proapoptotic proteins BAD and caspase-9 (12,13).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Inhibition of Inhibitor of Nuclear Factor-κB Phosphorylation Increases the Efficacy of Paclitaxel in in Vitro and in Vivo Ovarian Cancer Models

Mabuchi

Ohmichi

Nishio

et al. 2004

Clinical Cancer Research

Self Cite

162

137

View full text Add to dashboard Cite

show abstract

Section: Resultssupporting

confidence: 92%

Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Inhibition of Inhibitor of Nuclear Factor-κB Phosphorylation Increases the Efficacy of Paclitaxel in in Vitro and in Vivo Ovarian Cancer Models

Mabuchi

Ohmichi

Nishio

et al. 2004

Clinical Cancer Research

Self Cite

162

137

View full text Add to dashboard Cite

show abstract

“…As indicated in some reports, Taxol could directly induce phosphorylation of I-κBα (21). Several other studies have also shown that Taxol could directly activate survival pathways such as Bcl-2, Akt, Cox-2, mitogen-activated protein kinase, etc., independently of NF-κB (36,37). Transfection with an siRNA against IKKα and/or IKKβ could completely abolish parthenolide activity in this study, whereas the overexpression of IKKβ in cells could reverse the activity of parthenolide and showed significant Taxol resistance.…”

Section: Parthenolide Potentiates Chemosensitizationmentioning

confidence: 99%

Nuclear Factor-κB Inhibition by Parthenolide Potentiates the Efficacy of Taxol in Non–Small Cell Lung Cancer In vitro and In vivo

Zhang

Qiu²,

Jin³

et al. 2009

Molecular Cancer Research

View full text Add to dashboard Cite

In this study, we have examined the molecular events induced by parthenolide, a sesquiterpene lactone, and explored possible mechanisms of resistance and sensitization of tumor cells to Taxol. We showed that parthenolide could antagonize Taxol-mediated nuclear factor-κB (NF-κB) nuclear translocation and activation and Bcl-xl up-regulation by selectively targeting I-κB kinase activity. In A549 cells, inhibition of nuclear factor-κB by parthenolide resulted in activation of the mitochondrial death pathway to promote cytochrome c release and caspase 3 and 9 activation. In contrast, Taxol alone induced apoptosis via a pathway independent of mitochondria cytochrome c cascade. In addition, depletion of Bcl-xl rescued the apoptotic response to Taxol. Moreover, treatment with parthenolide increased the efficacy of the Taxol-induced inhibition of A549 tumor xenografts in mice. This study elucidated the cellular responses induced by parthenolide that decrease the threshold of mitochodriadependent apoptosis in the treatment of non-small cell lung cancer cells.

show abstract

“…PTX also activates the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway which positively impacts growth and is an important regulator of cap-dependent translation (Vivanco and Sawyers, 2002). Reportedly, PTX induces the phosphorylation of the proapoptotic protein, Bad, through the PI3K/Akt pathway, which negatively regulates its proapoptotic function (Mabuchi et al, 2002).…”

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

View full text Add to dashboard Cite

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.

show abstract

Inhibition of Phosphorylation of BAD and Raf-1 by Akt Sensitizes Human Ovarian Cancer Cells to Paclitaxel

Cited by 162 publications

References 65 publications

Inhibition of Inhibitor of Nuclear Factor-κB Phosphorylation Increases the Efficacy of Paclitaxel in in Vitro and in Vivo Ovarian Cancer Models

Inhibition of Inhibitor of Nuclear Factor-κB Phosphorylation Increases the Efficacy of Paclitaxel in in Vitro and in Vivo Ovarian Cancer Models

Nuclear Factor-κB Inhibition by Parthenolide Potentiates the Efficacy of Taxol in Non–Small Cell Lung Cancer In vitro and In vivo

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

Contact Info

Product

Resources

About