Adenovirus-mediated inhibition of NF-κB confers chemo-sensitization and apoptosis in prostate cancer cells

Flynn, Vincent J.; Ramanitharan, Anshiya; Moparty, Krishnarao; Davis, Rodney; Sikka, Suresh C.; Agrawal, Krishna C.; Abdel‐Mageed, Asim B.

doi:10.3892/ijo.23.2.317

Cited by 31 publications

(33 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to its role in prostate cancer behaviour (Andela et al, 2003), NF-kB activation is also implicated in chemo-and radioresistance. These observations are complemented by studies showing that NF-kB inhibition is a promising strategy for prostate cancer treatment, and, particularly, as a chemo-or radio-sensitisation strategy (Palayoor et al, 1999;Altuwaijri et al, 2003;Flynn et al, 2003;Kikuchi et al, 2003;Chendil et al, 2004). Clearly, inhibition of NF-kB may potentiate the antineoplastic effect of conventional chemotherapeutic agents (Sanchez-Perez et al, 2002).…”

Section: Discussionmentioning

confidence: 98%

Activation of nuclear factor-κB in human prostate carcinogenesis and association to biochemical relapse

et al. 2005

View full text Add to dashboard Cite

Nuclear factor (NF)-kB/p65 regulates the transcription of a wide variety of genes involved in cell survival, invasion and metastasis. We characterised by immunohistochemistry the expression of NF-kB/p65 protein in six histologically normal prostate, 13 high-grade prostatic intraepithelial neoplasia (PIN) and 86 prostate adenocarcinoma specimens. Nuclear localisation of p65 was used as a measure of NF-kB active state. Nuclear localisation of NF-kB was only seen in scattered basal cells in normal prostate glands. Prostatic intraepithelial neoplasias exhibited diffuse and strong cytoplasmic staining but no nuclear staining. In prostate adenocarcinomas, cytoplasmic NF-kB was detected in 57 (66.3%) specimens, and nuclear NF-kB (activated) in 47 (54.7%). Nuclear and cytoplasmic NF-kB staining was not correlated (P ¼ 0.19). By univariate analysis, nuclear localisation of NF-kB was associated with biochemical relapse (P ¼ 0.0009; log-rank test) while cytoplasmic expression did not. On multivariate analysis, serum preoperative prostate specific antigen (P ¼ 0.02), Gleason score (P ¼ 0.03) and nuclear NF-kB (P ¼ 0.002) were independent predictors of biochemical relapse. These results provide novel evidence for NF-kB/p65 nuclear translocation in the transition from PIN to prostate cancer. Our findings also indicate that nuclear localisation of NF-kB is an independent prognostic factor of biochemical relapse in prostate cancer.

show abstract

Section: Discussionmentioning

confidence: 98%

Activation of nuclear factor-κB in human prostate carcinogenesis and association to biochemical relapse

et al. 2005

View full text Add to dashboard Cite

show abstract

“…Microtubule cytoskeleton dysfunction has been shown to activate NF-kB (Rosette and Karin, 1995; Das and Mechanisms of IL-6 upregulation by paclitaxel T-H Wang et al White, 1997). Most recent reports have suggested activation of NF-kB to be an antiapoptotic mechanism of cancer cells (Dong et al, 2002;Uzzo et al, 2002;Dey et al, 2003;Flynn et al, 2003;Lin et al, 2004), although contrary observations have also been reported (Huang and Fan, 2002). Notably, NF-kB is also an important downstream transcription factor in the TLR4-MyD88 signaling cascade (Takeda et al, 2003) ( Figure 7).…”

Section: Discussionmentioning

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

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

“…A549/GR cells were also resistant to paclitaxel and docetaxel but not irinotecan and carboplatin. A recent report showed that there is a strong correction between NF-κB activation and gemcitabine-, paclitaxel-and docetaxel-resistance in several cancer cell lines (8)(9)(10). Curcumin, a yellow coloring agent in turmeric, has been shown to inhibit activation of NF-κB (11).…”

Section: Discussionmentioning

confidence: 99%

Isolation and characterization of gemcitabine-resistant human non-small cell lung cancer A549 cells

Ikeda

Vermeulen²,

Lau³

et al. 2011

Int J Oncol

View full text Add to dashboard Cite

Abstract.Gemcitabine is an effective chemotherapy against non-small cell lung cancer (NSCLC). However, resistance to gemcitabine reduces its efficacy. We have isolated gemcitabineresistant human non-small cell lung cancer A549 cells, termed A549/GR cells. A549/GR cells were resistant to gemcitabine as well as paclitaxel and docetaxel but not carboplatin and irinotecan. The expression level of multidrug resistance protein 7 (MRP7) in A549/GR cells was higher than that in A549 cells, and the inhibitor of MRP7 by cepharanthine increased the sensitivity to gemcitabine in A549/GR cells. These findings indicate that cepharanthine reversed gemcitabine resistance. To determine predictive molecular markers of gemcitabine resistance for more effective treatment of these tumors, we performed PCR array. We identified that CDKN1A/p21, CYP3A5, microsomal epoxide hyrolase 1 (EPHX1) and ABCC6 (MRP6) were up-regulated >5-fold in A549/GR cells. Gemcitabine also induced the expression of p21 and CYP3A5 in A549 cells. A better understanding of the characterization and mechanism of the resistance to gemcitabine in A549/GR cells may help identify agents that reverse clinical gemcitabine resistance in NSCLC.

show abstract

Adenovirus-mediated inhibition of NF-κB confers chemo-sensitization and apoptosis in prostate cancer cells

Cited by 31 publications

References 0 publications

Activation of nuclear factor-κB in human prostate carcinogenesis and association to biochemical relapse

Activation of nuclear factor-κB in human prostate carcinogenesis and association to biochemical relapse

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

Isolation and characterization of gemcitabine-resistant human non-small cell lung cancer A549 cells

Contact Info

Product

Resources

About