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

Mabuchi, Seiji; Ohmichi, Masahide; Nishio, Yukihiro; Hayasaka, Tadashi; Kimura, Akiko; Ohta, Tsuyoshi; Koyama, Jun; Takahashi, Kazuhiro; Yada-Hashimoto, Namiko; Seino-Noda, Hozumi; Sakata, Masahiro; Motoyama, Teiichi; Kurachi, Hirohisa; Testa, Joseph R.; Tasaka, Keiichi; Murata, Yuji

doi:10.1158/1078-0432.ccr-04-0958

Cited by 162 publications

(146 citation statements)

References 51 publications

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“…In relation to these data, PS-341 has been administrated alone or in combination to other drugs in multiple myeloma patients, refractory to conventional therapies [19]. Similar results obtained with other NF-kB inhibitors have been described in ovarian cancer [20], in acute myeloid leukemia [8], and in other neoplasia. In line with these data, we have shown that NF-kB inhibition may be a strategy to increase sensitivity to Etoposide-induced apoptosis in a cell line derived from a CML blast crisis.…”

Section: Discussionmentioning

confidence: 59%

NF‐kB inhibition as a strategy to enhance etoposide‐induced apoptosis in K562 cell line

et al. 2006

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Section: Discussionmentioning

confidence: 59%

NF‐kB inhibition as a strategy to enhance etoposide‐induced apoptosis in K562 cell line

et al. 2006

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“…Although the molecular basis of resistance to Taxol is not well-documented, mounting evidence supports the role of intrinsically or constitutively activated nuclear factor-κB (NF-κB) in affording protection against programmed cell death. Constitutive high levels of NF-κB activity have been detected in response to chemotherapy and radiation in ovarian cancer (3)(4)(5), pancreatic cancer (6), breast cancer (7,8), and prostate cancer (9). Our recent work has revealed that nuclear RelA and cytoplasmic pI-κBα are significantly associated with a poor prognosis in cancer (10).…”

Section: Introductionmentioning

confidence: 98%

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

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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.

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“…In addition, a broad array of actions independent of DNA adduct production has been described, including activation of mitochondrial (Biroccio et al, 2004) and Fas-associated apoptotic pathways (Razzaque et al, 1999) as well as induction of mitogen-activated protein kinases (MAPKs) (Zhang et al, 2005;Villedieu et al, 2006). Moreover, anti-invasive properties of cisplatin have been reported (Morikawa et al, 1995;Mabuchi et al, 2004) with the underlying mechanisms still being poorly understood.…”

mentioning

confidence: 99%

Upregulation of tissue inhibitor of matrix metalloproteinases-1 confers the anti-invasive action of cisplatin on human cancer cells

2007

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Cancer cell invasion is one of the crucial events in local spreading, growth and metastasis of tumors. The present study investigates the mechanism underlying the antiinvasive action of the chemotherapeutic cisplatin. In human cervical carcinoma cells (HeLa), cisplatin caused a time-and concentration-dependent suppression of cell invasion through Matrigel. Inhibition of invasion was accompanied by upregulation of tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), whereas levels of matrix metalloproteinase-2 (MMP-2), MMP-9 and TIMP-2 remained unchanged. Cisplatin's effects on TIMP-1 expression and invasion were associated with phosphorylations of p38 and p42/44 mitogen-activated protein kinases and were abrogated by specific inhibitors of both pathways. The impact of TIMP-1 in the anti-invasive action of cisplatin was proven by transfecting cells with small interfering RNA targeting TIMP-1, which completely reversed suppression of invasion by cisplatin. A functional relevance of TIMP-1 upregulation was substantiated by findings showing a concentration-dependent inhibition of Matrigel invasion by recombinant TIMP-1. The essential role of TIMP-1 in the anti-invasive action of cisplatin was confirmed using another human cervical carcinoma cell line (C33A) and human lung carcinoma cells (A549). Altogether, our data demonstrate a hitherto unknown mechanism by which cisplatin exerts its antimetastatic properties on highly invasive cancer cells.

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

Abstract: We investigated whether inhibition of nuclear factor-B (NF B) increases the efficacy of paclitaxel in in vitro

Cited by 162 publications

References 51 publications

NF‐kB inhibition as a strategy to enhance etoposide‐induced apoptosis in K562 cell line

NF‐kB inhibition as a strategy to enhance etoposide‐induced apoptosis in K562 cell line

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

Upregulation of tissue inhibitor of matrix metalloproteinases-1 confers the anti-invasive action of cisplatin on human cancer cells

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