Paclitaxel Induces Apoptosis Through Activation of Nuclear Protein Kinase C-δ and Subsequent Activation of Golgi Associated Cdk1 in Human Hormone Refractory Prostate Cancer

Lu, Pin-Hsuan; Chen, Yu; Chiang, Po-Cheng; Chen, Yi-Cheng; Ho, Yunn‐Fang; Kung, Fan-Lu; Guh, Jih‐Hwa

doi:10.1016/j.juro.2011.07.088

Cited by 16 publications

(12 citation statements)

References 28 publications

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“…The proapoptotic role of the protein tyrosine phosphatase PTPL1 in PC3 and LNCaP prostate cancer cells is PKC -dependent and induces inhibition of I B degradation and suppression of NF-B activity [420]. Several mechanisms are involved in PKC -dependent apoptosis, which is triggered by PMA, anticancer drugs, or androgens; these mechanisms include upregulation of DRs (e.g., DR5) [459], activation of DR downstream effectors (e.g., caspase-8 and -3, p38, and JNK) [459][460][461][462], enhanced release of death factors (e.g., TNF and/or TRAIL) [463,464], upregulation of ROCK (mediated by depletion of type I transmembrane protein p23/Tmp21) [460], and ROCK-mediated upregulation of p21…”

Section: Prostate Cancermentioning

confidence: 99%

Protein Kinase C (PKC) Isozymes and Cancer

Kang

2014

New Journal of Science

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Protein kinase C (PKC) is a family of phospholipid-dependent serine/threonine kinases, which can be further classified into three PKC isozymes subfamilies: conventional or classic, novel or nonclassic, and atypical. PKC isozymes are known to be involved in cell proliferation, survival, invasion, migration, apoptosis, angiogenesis, and drug resistance. Because of their key roles in cell signaling, PKC isozymes also have the potential to be promising therapeutic targets for several diseases, such as cardiovascular diseases, immune and inflammatory diseases, neurological diseases, metabolic disorders, and multiple types of cancer. This review primarily focuses on the activation, mechanism, and function of PKC isozymes during cancer development and progression.

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Section: Prostate Cancermentioning

confidence: 99%

Protein Kinase C (PKC) Isozymes and Cancer

Kang

2014

New Journal of Science

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“…PKCd is activated by genotoxins, oxidative stress, and death receptors, and its inhibition blocks apoptosis induced by a variety of stimuli in many cell types (6). In the case of prostate cancer, most reports indicate that PKCd expression is required to induce apoptosis by anticancer drugs or death receptors (8)(9)(10)(11)(12)(13)(14). Concretely, in a previous report, we documented that PKCd silencing induced apoptosis resistance to phenylethyl isothiocyanate and anti-Fas or paclitaxel treatments in PC3 and LNCaP cells, whereas the overexpression of PKCd improved apoptosis induced by these treatments in PC3 cells.…”

Section: Introductionmentioning

confidence: 99%

Loss of PKCδ Induces Prostate Cancer Resistance to Paclitaxel through Activation of Wnt/β-Catenin Pathway and Mcl-1 Accumulation

Flores

Castilla

Gasca

et al. 2016

Molecular Cancer Therapeutics

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Prostate cancer is the leading cause of cancer-related death among men in developed countries. Although castration therapy is initially effective, prostate cancers progress to hormone-refractory disease and in this case taxane-based chemotherapy is widely used. Castration-resistant prostate cancer cells often develop resistance to chemotherapy agents and the search for new therapeutic strategies is necessary. In this article, we demonstrate that PKCd silencing favors mitotic arrest after paclitaxel treatment in PC3 and LNCaP cells; however, this is associated with resistance to paclitaxel-induced apoptosis. In prostate cancer cells, PKCd seems to exert a proapoptotic role, acting as a negative regulator of the canonical Wnt/b-catenin pathway. PKCd silencing induces activation of Wnt/b-catenin pathway and the expression of its target genes, including Aurora kinase A, which is involved in activation of Akt and both factors play a key role in GSK3b inactivation and consequently in the stabilization of b-catenin and antiapoptotic protein Mcl-1. We also show that combined treatments with paclitaxel and Wnt/b-catenin or Akt inhibitors improve the apoptotic response to paclitaxel, even in the absence of PKCd. Finally, we observe that high Gleason score prostate tumors lose PKCd expression and this correlates with higher activation of b-catenin, inactivation of GSK3b, and higher levels of Aurora kinase A and Mcl-1 proteins. These findings suggest that targeting Wnt/b-catenin or Akt pathways may increase the efficacy of taxane chemotherapy in advanced human prostate cancers that have lost PKCd expression.

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“…According to our model, Paclitaxel was found to have a strong association score with prostate cancer. Indeed, the anti-neoplastic activity of Paclitaxel on prostate cancer was detected in many experiments [36,37]. The findings suggest that Paclitaxel induces nuclear translocation and activation of PKC-Îť, which in turn causes Golgi-Cdk1 activation.…”

Section: Discussionmentioning

confidence: 99%

Prediction of novel drug indications using network driven biological data prioritization and integration

et al. 2014

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BackgroundWith the rapid development of high-throughput genomic technologies and the accumulation of genome-wide datasets for gene expression profiling and biological networks, the impact of diseases and drugs on gene expression can be comprehensively characterized. Drug repositioning offers the possibility of reduced risks in the drug discovery process, thus it is an essential step in drug development.ResultsComputational prediction of drug-disease interactions using gene expression profiling datasets and biological networks is a new direction in drug repositioning that has gained increasing interest. We developed a computational framework to build disease-drug networks using drug- and disease-specific subnetworks. The framework incorporates protein networks to refine drug and disease associated genes and prioritize genes in disease and drug specific networks. For each drug and disease we built multiple networks using gene expression profiling and text mining. Finally a logistic regression model was used to build functional associations between drugs and diseases.ConclusionsWe found that representing drugs and diseases by genes with high centrality degree in gene networks is the most promising representation of drug or disease subnetworks.

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Paclitaxel Induces Apoptosis Through Activation of Nuclear Protein Kinase C-δ and Subsequent Activation of Golgi Associated Cdk1 in Human Hormone Refractory Prostate Cancer

Cited by 16 publications

References 28 publications

Protein Kinase C (PKC) Isozymes and Cancer

Protein Kinase C (PKC) Isozymes and Cancer

Loss of PKCδ Induces Prostate Cancer Resistance to Paclitaxel through Activation of Wnt/β-Catenin Pathway and Mcl-1 Accumulation

Prediction of novel drug indications using network driven biological data prioritization and integration

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