A JNK inhibitor SP600125 induces defective cytokinesis and enlargement in P19 embryonal carcinoma cells

Nakaya, Kohei; Ooishi, Ryo; Funaba, Masayuki; Murakami, Masaru

doi:10.1002/cbf.1597

Cited by 7 publications

(8 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Up to date, there are contrasting reports about p53 involvement in the SP mechanism of action [ 11 , 13 - 15 , 27 ]. To elucidate this point, three cell lines representing different TP53 status were chosen for further examination: the TP53 wild-type TPC1, the TP53 p.P152L mutant HTC/C3, and the p53 pseudo-null SW1736.…”

Section: Resultsmentioning

confidence: 99%

“…The presence of nuclear abnormalities such as heterochromatic foci, multinucleation and nuclear blebbing, lysosomal compartment expansion and positive γ-H2A.X staining in a large fraction of SP treated HTC/C3 cells ( Supplementary Figure 2 ) confirmed the presence of cellular senescence [ 31 - 32 ]. To date, increases in cell dimensions and in p21 expression following SP treatment have been occasionally reported [ 27 , 33 ]. On the other hand, SP-induced p53-dependent premature senescence has never been reported.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

SP600125 has a remarkable anticancer potential against undifferentiated thyroid cancer through selective action on ROCK and p53 pathways

et al. 2015

View full text Add to dashboard Cite

Thyroid cancer is the most common endocrine malignancy with increasing incidence worldwide.The majority of thyroid cancer cases are well differentiated with favorable outcome. However, undifferentiated thyroid cancers are one of the most lethal human malignancies because of their invasiveness, metastatization and refractoriness even to the most recently developed therapies.In this study we show for the first time a significant hyperactivation of ROCK/HDAC6 pathway in thyroid cancer tissues, and its negative correlation with p53 DNA binding ability.We demonstrate that a small compound, SP600125 (SP), is able to induce cell death selectively in undifferentiated thyroid cancer cell lines by specifically acting on the pathogenic pathways of cancer development. In detail, SP acts on the ROCK/HDAC6 pathway involved in dedifferentiation and invasiveness of undifferentiated human cancers, by restoring its physiological activity level. As main consequence, cancer cell migration is inhibited and, at the same time, cell death is induced through the mitotic catastrophe. Moreover, SP exerts a preferential action on the mutant p53 by increasing its DNA binding ability. In TP53-mutant cells that survive mitotic catastrophe this process results in p21 induction and eventually lead to premature senescence. In conclusion, SP has been proved to be able to simultaneously block cell replication and migration, the two main processes involved in cancer development and dissemination, making it an ideal candidate for developing new drugs against anaplastic thyroid cancer.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

SP600125 has a remarkable anticancer potential against undifferentiated thyroid cancer through selective action on ROCK and p53 pathways

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Cyclin dependent kinases (CDKs) are the key cell cycle regulators 11 21 . The CDK inhibitor, p21, has been reported to have different expression levels in normal diploid and non-diploid cells (such as cancer cells) as the downstream of the p53 signal pathway 12 21 . Our study reveals that both p21 and p53 expressions are up-regulated in the SP600125-induced tetraploid cells, especially compared with the diploid cells.…”

Section: Discussionmentioning

confidence: 99%

“…Previous results indicate that the small compound SP600125 could induce polyploidization of mammalian cancer cells 11 12 . As a c-Jun N-terminal kinase (Jnk) inhibitor, it is reported that SP600125 can lead to G2/M phase arrest such that G2-to-M phase transition is prevented, and DNA endoreplication occurs directly from the G2 phase 11 13 14 .…”

mentioning

confidence: 96%

Autotetraploid cell Line induced by SP600125 from crucian carp and its developmental potentiality

Zhou

Wang

Jiang

et al. 2016

Sci Rep

View full text Add to dashboard Cite

Polyploidy has many advantages over diploidy, such as rapid growth, sterility, and disease resistance, and has been extensively applied in agriculture and aquaculture. Though generation of new polyploids via polyploidization has been achieved in plants by different ways, it is comparatively rare in animals. In this article, by a chemical compound, SP600125, polyploidization is induced in fish cells in vitro, and a stable autotetraploid cell line has been generated from diploid fibroblast cells of crucian carp. As a c-Jun N-terminal kinase (Jnk) inhibitor, SP600125 does not function during the induction process of polyploidization. Instead, the p53 signal pathway might be involved. Using the SP600125-induced tetraploid cells and eggs of crucian carp as the donors and recipients, respectively, nuclear transplantation was conducted such that tetraploid embryos were obtained. It suggests that combining polyploidization and the somatic cell nuclear transfer technique (SCNT) is an efficient way to generate polyploidy, and the presented method in this research for generating the tetraploid fish from diploid fish can provide a useful platform for polyploid breeding.

show abstract

“…Another study showed that SP induces defective cytokinesis and enlargement of P19 cells [36]. These results could be used to argue that the SP-induced increase in MOR expression is caused by the presence of increased DNA content and increased stability of the MOR mRNA.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of c-Jun NH2-terminal kinase stimulates mu opioid receptor expression via p38 MAPK-mediated nuclear NF-κB activation in neuronal and non-neuronal cells

Wagley

Hwang

Lin

et al. 2013

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

View full text Add to dashboard Cite

Despite its potential side effects of addiction, tolerance and withdrawal symptoms, morphine is widely used for reducing moderate and severe pain. Previous studies have shown that the analgesic effect of morphine depends on mu opioid receptor (MOR) expression levels, but the regulatory mechanism of MOR is not yet fully understood. Several in vivo and in vitro studies have shown that the c-Jun NH2-terminal kinase (JNK) pathway is closely associated with neuropathic hyperalgesia, which closely resembles the neuroplastic changes observed with morphine antinociceptive tolerance. In this study, we show that inhibition of JNK by SP600125, its inhibitory peptide, or JNK-1 siRNA induced MOR at both mRNA and protein levels in neuronal cells. This increase in MOR expression was reversed by inhibition of the p38 mitogen-activated protein kinase (MAPK) pathway, but not by inhibition of the mitogen-activated protein/extracellular signal-regulated kinase (MEK) pathway. Further experiments using cell signaling inhibitors showed that MOR upregulation by JNK inhibition involved nuclear factor-kappa B (NF-κB). The p38 MAPK dependent phosphorylation of p65 NF-κB subunit in the nucleus was increased by SP600125 treatment. We also observed by chromatin immunoprecipitation (ChIP) analysis that JNK inhibition led to increased bindings of CBP and histone-3 dimethyl K4, and decreased bindings of HDAC-2, MeCP2, and histone-3 trimethyl K9 to the MOR promoter indicating a transcriptional regulation of MOR by JNK inhibition. All these results suggest a regulatory role of the p38 MAPK and NF-κB pathways in MOR gene expression and aids to our better understanding of the MOR gene regulation.

show abstract

A JNK inhibitor SP600125 induces defective cytokinesis and enlargement in P19 embryonal carcinoma cells

Cited by 7 publications

References 30 publications

SP600125 has a remarkable anticancer potential against undifferentiated thyroid cancer through selective action on ROCK and p53 pathways

SP600125 has a remarkable anticancer potential against undifferentiated thyroid cancer through selective action on ROCK and p53 pathways

Autotetraploid cell Line induced by SP600125 from crucian carp and its developmental potentiality

Inhibition of c-Jun NH2-terminal kinase stimulates mu opioid receptor expression via p38 MAPK-mediated nuclear NF-κB activation in neuronal and non-neuronal cells

Contact Info

Product

Resources

About